==================================BSR21==================================
21. Association of free fatty acids with phospholipid bilayers.
Fatty acids- aqueous phase, hydrated fatty acids (Fatty acids
associated with water).
Ionization of fatty acids to acid-soaps.
1
UI - 87111863
AU - Takagi M ; Higashioka H ; Morita N
TI - Effects of lipophilic derivatives of L-ascorbic acid and
dehydro-L-ascorbic acid on the peroxidation of linoleic acid in neutral
phosphate buffer containing alcohol.
AB - 6-O-Palmitoyl-AsA (AP) and -DHA (DHAP) suppressed LA peroxidation
considerably in both 10% and 20% EtOH solutions. The duration of the
suppression of LA peroxidation was longer with AP than with DHAP. But
after the initial suppression of LA peroxidation, both derivatives showed
an accelerating effect. 6-O-Acetyl-AsA (Ac-AsA) and -DHA (Ac-DHA)
accelerated LA peroxidation from the start of the reaction in 10% EtOH,
but suppressed it notably in 20% EtOH.
4-Phenyl-2,3-dihydroxy-2-buten-4-olide (PDHB) and
4-phenyl-2,3-dioxo-4-butenolide (PDOB) accelerated LA peroxidation in 10%
EtOH. With 20% EtOH solution, PDHB suppressed LA peroxidation notably, as
did AP, but PDOB showed only a short duration (about 1 h) of suppression.
These results suggest the complexity of LA peroxidation catalyzed by
lipophilic AsA or DHA in aqueous solution containing alcohol.
MH - *Alcohol, Ethyl ; Ascorbic Acid/*ANALOGS & DERIVATIVES/PHARMACODYNAMICS ;
Buffers ; Dehydroascorbic Acid/*PHARMACODYNAMICS ; *Linoleic Acids ;
*Lipid Peroxides ; Oxidation-Reduction ; Phosphates ; 4-Butyrolactone/
ANALOGS & DERIVATIVES/PHARMACODYNAMICS
SO - J Nutr Sci Vitaminol (Tokyo) 1986 Aug;32(4):389-94
2
UI - 87101036
AU - Froud RJ ; East JM ; Rooney EK ; Lee AG
TI - Binding of long-chain alkyl derivatives to lipid bilayers and to
(Ca2+-Mg2+)-ATPase.
AB - Binding constants for myristoleic, palmitoleic, palmitic, oleic, and
eicosanoic acids and oleyland stearylamine to lipid bilayers have been
determined by using microelectrophoresis. Quenching of the fluorescence
of the hydrophobic tryptophan analogue N-palmitoyl-L-tryptophan n-hexyl
ester incorporated into lipid bilayers by oleic acid and oleylamine and
their brominated derivatives is interpreted in terms of unlimited binding
to the bilayers. The tryptophan fluorescence of the (Ca2+-Mg2+)-ATPase
purified from sarcoplasmic reticulum is quenched when reconstituted into
bilayers of 1,2-bis(9,10-dibromostearoyl)-phosphatidylcholine (BRPC).
Addition of fatty acids, oleylamine, oleyl alcohol, and methyl oleate to
the ATPase reconstituted with BRPC reduces the quenching caused by BRPC,
indicating binding of these molecules at the lipid-protein interface
(annular sites). The charged molecules bind more strongly at the annular
sites than do the uncharged molecules. Additional quenching of
BRPC-ATPase by brominated derivatives of these molecules indicates
binding at sites distinct from the lipid-protein interface, with binding
constants similar to those for binding at annular sites, except for
oleylamine. Quenching of tryptophan fluorescence of the ATPase by fatty
acids and oleylamine suggests that ca. 50% of the tryptophan residues of
the ATPase are located close to the lipid-water interface of the
membrane.
MH - Adenosine Triphosphatase, Calcium/*METABOLISM ; Adenosine Triphosphatase,
Magnesium/*METABOLISM ; Animal ; *Fatty Acids/METABOLISM ; Hydrogen-Ion
Concentration ; Kinetics ; *Lipid Bilayers ; Muscles/ENZYMOLOGY ;
*Phosphatidylcholines ; Protein Binding ; Rabbits ; Structure-Activity
Relationship ; Support, Non-U.S. Gov't ; Tryptophan/ANALOGS & DERIVATIVES
SO - Biochemistry 1986 Nov 18;25(23):7535-44
3
UI - 87098794
AU - Maiorino M ; Roveri A ; Gregolin C ; Ursini F
TI - Different effects of Triton X-100, deoxycholate, and fatty acids on the
kinetics of glutathione peroxidase and phospholipid hydroperoxide
glutathione peroxidase.
AB - The effects of Triton X-100, deoxycholate, and fatty acids were studied
on the two steps of the ping-pong reaction catalyzed by Se-dependent
glutathione peroxidases. The study was carried out by analyzing the
single progression curves where the specific glutathione oxidation was
monitored using glutathione reductase and NADPH. While the "classic:
glutathione peroxidase was inhibited only by Triton, the newly discovered
"phospholipid hydroperoxide glutathione peroxidase: was inhibited by
deoxycholate and by unsaturated fatty acids. The kinetic analysis showed
that in the case of glutathione peroxidase only the interaction of the
lipophilic peroxidic substrate was hampered by Triton, indicating that
the enzyme is not active at the interface. Phospholipid hydroperoxide
glutathione peroxidase activity measured with linoleic acid hydroperoxide
as substrate, on the other hand, was not stimulated by the Triton
concentrations which have been shown to stimulate the activity on
phospholipid hydroperoxides. Furthermore a slight inhibition was apparent
at high Triton concentrations and the effect could be attributed to a
surface dilution of the substrate. Deoxycholate and unsaturated fatty
acids were not inhibitory on glutathione peroxidase but inhibited both
steps of the peroxidic reaction of phospholipid hydroperoxide glutathione
peroxidase, in the presence of either amphiphilic or hydrophilic
substrates. This inhibition pattern suggests an interaction of anionic
detergents with the active site of this enzyme. These results are in
agreement with the different roles played by these peroxidases in the
control of lipid peroxide concentrations in the cells. While glutathione
peroxidase reduces the peroxides in the water phase (mainly hydrogen
peroxide), the new peroxidase reduces the amphyphilic peroxides, possibly
at the water-lipid interface.
MH - Binding Sites ; Catalysis ; Comparative Study ; Deoxycholic Acid/
*PHARMACODYNAMICS ; Fatty Acids/*PHARMACODYNAMICS ; Glutathione
Peroxidase/ANTAGONISTS & INHIBITORS/*METABOLISM ; Kinetics ; Linoleic
Acids/METABOLISM ; Lipid Peroxides/METABOLISM ; Oleic Acids/
PHARMACODYNAMICS ; Polyethylene Glycols/*PHARMACODYNAMICS ; Substrate
Specificity
SO - Arch Biochem Biophys 1986 Dec;251(2):600-5
USER:
4
UI - 87076616
AU - Fern:andez MS ; Gonz:alez-Mart:inez MT ; Calder:on E
TI - The effect of pH on the phase transition temperature of
dipalmitoylphosphatidylcholine-palmitic acid liposomes.
AB - The shift in the gel-liquid crystal phase transition temperature (tm) of
dipalmitoylphosphatidylcholine liposomes induced by incorporation of 10
mol% palmitic acid, was measured by 90 degrees light scattering at
different bulk pH values. It has been found that the tm shift decreases
sigmoidally from 4.7 to -0.3 degrees C as the bulk pH is raised from 5 to
11. Since it is in this range that the carboxyl group of a membrane-bound
fatty acid should ionize, our results can be interpreted to mean that
there is relationship between the tm shift and the degree of dissociation
of palmitic acid, the uncharged fatty acid increasing tm and its
conjugate, anionic form, slightly decreasing the transition temperature
of dipalmitoylphosphatidylcholine liposomes. The experimental results are
fitted by a modified form of the Henderson-Hasselbach equilibrium
expression which takes into account the effect of the anionic fatty acid
on the surface potential and hence, on the surface pH of liposomes,
according to Gouy-Chapman and Boltzmann equations, respectively. Best fit
between theory and experiments is found when the intrinsic interfacial pK
of palmitic acid is set equal to 7.7. This high pK value can be explained
as due to the effect of the lower dielectric constant of the interfacial
region, as compared to bulk water, on the acid-base dissociation of the
carboxyl group. The results presented here show that upon incorporation
of palmitic acid, the phase transition of dipalmitoylphosphatidylcholine
bilayers becomes extremely sensitive to changes of pH in the vicinity of
the physiological range. This property is not shown by the pure
phospholipid bilayers in the same pH range.
MH - Hydrogen-Ion Concentration ; Light ; *Liposomes ; *Palmitic Acids ;
Scattering, Radiation ; Support, Non-U.S. Gov't ; Temperature ;
*1,2-Dipalmitoylphosphatidylcholine
SO - Biochim Biophys Acta 1986 Dec 16;863(2):156-64
5
UI - 87054645
AU - Navar LG ; Paul RV ; Carmines PK ; Chou CL ; Marsh DJ
TI - Intrarenal mechanisms mediating pressure natriuresis: role of angiotensin
and prostaglandins.
AB - The ability of the kidney to increase sodium and water excretion in
response to increases in perfusion pressure has been recognized for more
than 50 years. Because glomerular filtration rate is tightly
autoregulated, pressure natriuresis occurs as the result of decreased
tubular sodium reabsorption rather than increased filtered load.
Micropuncture and microperfusion data support the contention that acute
changes in arterial pressure can alter proximal tubule reabsorption;
however, studies have failed to show a consistent association between
changes in sodium excretion and peritubular, interstitial, or tubular
pressures. Thus, the specific intrarenal mechanism for the change in
tubular reabsorption in response to an acute change in arterial pressure
does not appear to be related to the peritubular physical factors at the
level of outer cortical nephrons. The possible roles of angiotensin and
prostaglandins as humoral mediators of pressure natriuresis are
considered in this report. Although angiotensin II is a powerful
modulator of the slope of the pressure natriuresis relationship, the
responsiveness of sodium excretion to arterial pressure is actually
enhanced by angiotensin-converting enzyme inhibitors. These data suggest
that angiotensin does not mediate the basic phenomenon. Recent
experiments indicate that intrarenal prostaglandins also modulate the
magnitude of the pressure natriuresis relationship, but these hormones do
not appear to be essential for its basic manifestation.
MH - Absorption ; Angiotensin II/*PHYSIOLOGY ; Animal ; *Blood Pressure ;
Human ; Kidney Tubules, Proximal/PHYSIOLOGY ; Kidney/BLOOD SUPPLY/
*PHYSIOLOGY ; *Natriuresis ; Prostaglandins/*PHYSIOLOGY ;
Renin-Angiotensin System ; Review ; Support, U.S. Gov't, P.H.S.
SO - Fed Proc 1986 Dec;45(13):2885-91
6
UI - 87049759
AU - Connor J ; Norley N ; Huang L
TI - Biodistribution of pH-sensitive immunoliposomes.
AB - Liposomes composed of either dioleoylphosphatidylethanolamine and oleic
acid (pH-sensitive) or dioleoylphosphatidylcholine and oleic acid
(pH-insensitive) were injected into C3H and Balb/c mice in order to
determine the tissue distribution of both the lipid and the aqueous
content. The lipid component was monitored by use of [3H]cholestanyl
ether and the aqueous content was monitored by use of encapsulated
125I-tyraminyl-inulin. The pH-insensitive liposomes injected into both
types of mice were rapidly cleared from the blood stream followed by
accumulation primarily in the liver, followed by the spleen. The presence
of a monoclonal antibody on the liposome surface caused a slight
acceleration in liver accumulation, though generally gave the same
profile as the antibody-free liposomes. pH-sensitive liposomes were leaky
upon exposure to the mouse plasma following injection. The lipid
component, though, displayed a large amount (e.g., 50-70% in C3H mice) of
accumulation in the lung for up to 6 h, followed by a subsequent
appearance in the liver and spleen. The presence of monoclonal antibody
had no effect on the tissue distribution profile. These results indicate
that the pH-sensitive liposomes, although ineffective as an aqueous drug
delivery agent, may be effective as a means of delivering lipophilic
drugs to the lung.
MH - Animal ; Antibodies, Monoclonal/*ADMINISTRATION & DOSAGE ; Hydrogen-Ion
Concentration ; Inulin/ANALOGS & DERIVATIVES ; Iodine Radioisotopes ;
Liposomes/*ADMINISTRATION & DOSAGE ; Mice ; Mice, Inbred BALB C ; Mice,
Inbred C3H ; Oleic Acids/*ADMINISTRATION & DOSAGE ; Phosphatidylcholines/
*ADMINISTRATION & DOSAGE ; Phosphatidylethanolamines/*ADMINISTRATION &
DOSAGE ; Support, U.S. Gov't, P.H.S. ; Tissue Distribution
SO - Biochim Biophys Acta 1986 Dec 10;884(3):474-81
7
UI - 87049749
AU - Turk J ; Wolf BA ; Lefkowith JB ; Stump WT ; McDaniel ML
TI - Glucose-induced phospholipid hydrolysis in isolated pancreatic islets:
quantitative effects on the phospholipid content of arachidonate and
other fatty acids.
AB - Our recent findings indicate that glucose-induced insulin secretion from
isolated pancreatic islets is temporally associated with accumulation of
substantial amounts of free arachidonic acid and that arachidonate may
serve as a second messenger for intracellular calcium mobilization in
islets. In an effort to determine the source of this released
arachidonate, the endogenous fatty acid composition of phospholipids from
islets has been determined by thin-layer chromatographic separation of
the phospholipids, methanolysis to the fatty acid methyl esters, and
quantitative gas chromatographic analyses. The relative abundance of
phospholipids in islets as judged by their fatty acid content was
phosphatidylcholine (PC), 0.63; phosphatidylethanolamine (PE), 0.23;
phosphatidylinositol (PI), 0.067; phosphatidylserine (PS), 0.049.
Arachidonate constituted 17% of the total islet fatty acid content, and
PC contained 43% of total islet arachidonate. Islets incubated with
[3H]arachidonate in the presence of 28 mM D-glucose incorporated
radiolabel into PC with a considerably higher specific activity than that
of PE, PS or PI. The total fatty acid content of PC from islets incubated
with 28 mM glucose for 30 min was significantly lower than that of islets
incubated with 3 mM glucose, and smaller effects were observed with PE,
PS and PI. The molar decrement in PC arachidonate was 3.2 pmol/islet
under these conditions, which is sufficient to account for the previously
observed accumulation of free arachidonate (2 pmol/islet). A sensitive
method involving negative ion-chemical ionization-mass spectrometric
analyses of the pentafluorobenzyl esters of fatty acids derived from
trace amounts of lysophosphatidylcholine (lyso-PC) was developed, and
glucose-stimulation was found to reduce islet lyso-PC content by about
10-fold. These findings indicate that the insulin secretagogue D-glucose
induces phospholipid hydrolysis in islets and suggest that PC may be the
major source of free arachidonate which accumulates in glucose-stimulated
islets.
MH - Animal ; Arachidonic Acids/*METABOLISM ; Cells, Cultured ; Fatty Acids/
*METABOLISM ; Glucose/*PHARMACODYNAMICS ; Hydrolysis ; In Vitro ; Islands
of Langerhans/DRUG EFFECTS/*METABOLISM ; Kinetics ; Male ; Phospholipids/
*METABOLISM ; Rats ; Rats, Inbred Strains ; Support, U.S. Gov't, P.H.S.
SO - Biochim Biophys Acta 1986 Dec 5;879(3):399-409
8
UI - 87049619
AU - Ho RJ ; Rouse BT ; Huang L
TI - Target-sensitive immunoliposomes: preparation and characterization.
AB - A novel target-sensitive immunoliposome was prepared and characterized.
In this design, target-specific binding of antibody-coated liposomes was
sufficient to induce bilayer destabilization, resulting in a
site-specific release of liposome contents. Unilamellar liposomes were
prepared by using a small quantity of palmitoyl-immunoglobulin G (pIgG)
to stabilize the bilayer phase of the unsaturated
dioleoylphosphatidylethanolamine (PE) which by itself does not form
stable liposomes. A mouse monoclonal IgG antibody to the glycoprotein D
of Herpes simplex virus (HSV) and PE were used in this study. A minimal
coupling stoichiometry of 2.2 palmitic acids per IgG was essential for
the stabilization activity of pIgG. In addition, the minimal pIgG to PE
molar ratio for stable liposomes was 2.5 X 10(-4). PE immunoliposomes
bound with HSV-infected mouse L929 cells with an apparent Kd of 1.00 X
10(-8) M which was approximately the same as that of the native antibody.
When 50 mM calcein was encapsulated in the PE immunoliposomes as an
aqueous marker, binding of the liposomes to HSV-infected cells resulted
in a cell concentration dependent lysis of the liposomes as detected by
the release of the encapsulated calcein. Neither uninfected nor Sendai
virus infected cells caused a significant amount of calcein release.
Therefore, the release of calcein from PE immunoliposomes was target
specific. Dioleoylphosphatidylcholine immunoliposomes were not lysed upon
contact with infected cells under the same conditions, indicating that PE
was essential for the target-specific liposome destabilization.(ABSTRACT
TRUNCATED AT 250 WORDS)
MH - Animal ; Cell Transformation, Viral ; Deoxycholic Acid ; Herpesvirus
Hominis/GENETICS ; *IgG ; L Cells/METABOLISM ; Lipid Bilayers ;
*Liposomes ; Mice ; *Palmitic Acids ; Para-Influenza Virus Type 1/
GENETICS ; Peptide Hydrolases/METABOLISM ; *Phosphatidylcholines ;
*Phosphatidylethanolamines ; Support, Non-U.S. Gov't ; Support, U.S.
Gov't, P.H.S. ; Tritium
SO - Biochemistry 1986 Sep 23;25(19):5500-6
9
UI - 87017195
AU - Brash AR ; Ingram CD
TI - Lipoxygenase metabolism of endogenous and exogenous arachidonate in
leukocytes: GC-MS analyses of incubations in H2(18)O buffers.
AB - Fatty acids are labeled with 18O in the carboxyl group during ester
hydrolysis in H2(18)O. We utilized this principle to develop a novel mass
spectrometric method for study of the turnover of arachidonic acid in
intact cell systems. Analysis of 18O incorporations was by negative ion
chemical ionization GC-MS. The use of deuterium-labeled exogenous
substrates allowed the metabolic fate of exogenous and intrinsic
compounds to be distinguished. Thus, it was shown that the preferred
route of 5-lipoxygenase metabolism of exogenous arachidonic acid in
ionophore-stimulated human neutrophils is via direct reaction with the
enzyme and not via incorporation into cellular lipids. The re-uptake of
5-HETE was also studied. For investigation of intracellular reactions
which involve ester hydrolysis, the 18O labeling method is unique in
providing direct evidence of the intermediate metabolic pathway of
endogenous and exogenous products associated with the arachidonic acid
cascade.
MH - A-23187/PHARMACODYNAMICS ; Arachidonic Acids/ADMINISTRATION & DOSAGE/
*METABOLISM ; Deuterium/DIAGNOSTIC USE ; Esters ; Human ; Hydrolysis ;
Hydroxyeicosatetraenoic Acids/ANALYSIS/METABOLISM ; Lipoxygenases/
*METABOLISM ; Mass Fragmentography ; Neutrophils/*METABOLISM ; Support,
U.S. Gov't, P.H.S.
SO - Prostaglandins Leukotrienes Med 1986 Aug;23(2-3):149-54
10
UI - 87013827
AU - Tarapoom N ; Royce R ; Yorio T
TI - Inhibition of the antidiuretic hormone hydroosmotic response by
phospholipids and phospholipid metabolites.
AB - Phospholipid metabolities and phospholipids containing arachidonic acid
(AA) inhibited the antidiuretic hormone (ADH)-induced increase in
transepithelial water flow in the toad urinary bladder, but had no effect
on basal water flow when added to the serosal bathing solution. Other
fatty acid-substituted phospholipid metabolites had no effect on osmotic
water movement in the presence or absence of ADH. Indomethacin attenuated
the inhibitory effects of the AA containing phospholipid metabolities
(PMAA), suggesting that the PMAA response required AA release and
prostaglandin (PG) formation. PMAA increased PGE formation as measured by
radioimmunoassay. PG have been reported to inhibit ADH-stimulated water
flow by inhibiting adenylcyclase. PGE2 (10(-8) M) had no effect on cyclic
AMP-stimulated water flow, whereas exogenous AA and PMAA attenuated the
hydroosmotic response to added cyclic AMP. Indomethacin only partially
reversed the inhibition by AA of the cyclic AMP-associated water
movement, suggesting that the inhibition by AA and PMAA may involve other
metabolites of AA than PG. PG and the AA cascade have been implicated as
cellular modulators of the ADH hydroosmotic response. The present results
offer additional support to the theory that this system may regulate the
intracellular events that are transduced following receptor activation by
ADH.
MH - Adenosine Cyclic Monophosphate/PHARMACODYNAMICS ; Animal ; Arachidonic
Acids/*PHARMACODYNAMICS ; Argipressin/ANTAGONISTS & INHIBITORS/
*PHARMACODYNAMICS ; Bladder/DRUG EFFECTS/*PHYSIOLOGY ; Body Water/
METABOLISM ; Bufo Marinus ; Epithelium/DRUG EFFECTS/PHYSIOLOGY ; In Vitro
; Indomethacin ; Osmolar Concentration ; Phospholipids/*PHARMACODYNAMICS
; Structure-Activity Relationship ; Support, Non-U.S. Gov't ; Support,
U.S. Gov't, P.H.S.
SO - Lipids 1986 Sep;21(9):596-602
11
UI - 87005916
AU - Okun IM ; Merezhinskaya NV ; Rakovich AA ; Volkovets TM ; Aksentsev SL ;
Konev SV
TI - Inactivation of muscarinic acetylcholine receptors in brain synaptic
membranes by free fatty acids. Evaluation of the role of lipid phase.
AB - Arachidonic, linolenic and linoleic acids decreased the binding of the
m-cholinergic antagonist [3H] QNB and did not affect the ratio of high to
low affinity binding sites to the agonist carbamoylcholine in rat brain
synaptic membranes. In the presence of arachidonic acid, SH-reagent
N-ethylmaleimide acquired the ability to block QNB binding to receptor.
Lipids in the bilayer and annular regions were probed by fluorescence of
1,6-diphenyl-1, 3, 5-hexatriene and pyrene. A microviscosity drop induced
by increasing temperature from 10 to 37 degrees C did not affect the
level of QNB equilibrium binding, whereas arachidonic acid strongly
inhibited the binding at concentrations inducing the same drop in
microviscosity as that induced by heating. For various unsaturated fatty
acids an equal extent of receptor blocking was reached at quite different
degrees of bilayer fluidization, the state of annular lipid being not
changed under these conditions. It is suggested that the effect of
unsaturated acids is reached through their direct interaction with the
receptor, which undergoes a conformational change, rather than by an
alteration of the physical state of the lipid phase of the membrane.
MH - Animal ; *Brain Chemistry ; Carbachol/METABOLISM ; Fatty Acids,
Nonesterified/*PHARMACODYNAMICS ; Lipid Bilayers/METABOLISM ; Membrane
Fluidity/DRUG EFFECTS ; Membrane Lipids/*PHYSIOLOGY ; Quinuclidinyl
Benzilate/METABOLISM ; Rats ; Receptors, Muscarinic/*DRUG EFFECTS ;
Spectrometry, Fluorescence ; Synaptic Membranes/*METABOLISM
SO - Gen Physiol Biophys 1986 Jun;5(3):243-58
12
UI - 86250481
AU - Selig WM ; Noonan TC ; Kern DF ; Malik AB
TI - Pulmonary microvascular responses to arachidonic acid in isolated
perfused guinea pig lung.
AB - We examined the effects of arachidonic acid (AA) on pulmonary
hemodynamics and fluid balance in Ringer- and blood-perfused guinea pig
lungs during constant-flow conditions. Mean pulmonary arterial (Ppa),
venous (Pv), and capillary pressures (Pcap, estimated by the
double-occlusion method) were measured, and arterial (Ra) and venous
resistances (Rv) were calculated. Bolus AA injection (500 micrograms)
caused transient increases (peak response 1 min post-AA) in Ppa, Pcap,
and Rv without affecting Ra in both Ringer- and blood-perfused lungs. The
response was sustained in blood-perfused lungs. AA had no effect on the
capillary filtration coefficient in either Ringer- or blood-perfused
lungs. AA stimulated the release of thromboxane B2 and
6-ketoprostaglandin F1 alpha in both Ringer- and blood-perfused lungs,
but the responses were sustained only in the blood-perfused lungs.
Meclofenamate (1.5 X 10(-4) M), a cyclooxygenase inhibitor, abolished the
AA-induced pulmonary hemodynamic responses in both Ringer- and
blood-perfused lungs, whereas U-60257 (10 microM), a lipoxygenase
inhibitor, attenuated the response only in the blood-perfused lungs. In
conclusion, AA does not alter pulmonary vascular permeability to water in
either Ringer- or blood-perfused lungs. AA mediates pulmonary
venoconstriction and thus contributes to the rise in Pcap. The
venoconstriction results from the generation of cyclooxygenase-derived
metabolites from lung parenchymal cells and blood-formed elements.
Lipoxygenase metabolites may also contribute to the vasoconstriction in
the blood-perfused lungs.
MH - Animal ; Arachidonic Acids/*PHARMACODYNAMICS ; Blood Pressure/DRUG
EFFECTS ; Female ; Guinea Pigs ; In Vitro ; Lung ; Meclofenamic Acid/
PHARMACODYNAMICS ; Microcirculation/DRUG EFFECTS ; Osmolar Concentration
; Perfusion ; Prostaglandins X/PHARMACODYNAMICS ; Pulmonary Circulation/
*DRUG EFFECTS ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. ;
Thromboxane B2/METABOLISM ; Vascular Resistance/DRUG EFFECTS ;
6-Ketoprostaglandin F1 alpha/METABOLISM
SO - J Appl Physiol 1986 Jun;60(6):1972-9
13
UI - 86316786
AU - Allen HR ; Tucker RK ; Geren CR
TI - Potentiation of the toxicity of basic peptides from rattlesnake venoms by
sodium acetate.
AB - The potentiating effect of sodium acetate on the toxicity of crotamine
from Crotalus durissus terrificus venom, E toxin from Crotalus horridus
horridus venom, and myotoxin a from Crotalus viridus viridis venom was
examined. Subcutaneous injection of 6.3 mg/kg body weight of either
crotamine or E toxin in 0.6 ml of water or myotoxin a in 0.6 ml of 0.05 M
Tris/0.1 M NaCl buffer, pH 9.0, failed to produce lethality in mice.
Injection of either E toxin or crotamine at doses of 4.0 mg/kg in 0.6 ml
of 20 mM phosphate, pH 7.2, containing 1 M sodium chloride also failed to
produce lethality. However, when any of the toxins were injected in 0.4
ml of 1 M sodium acetate, pH 7.0, lethality was observed. LD50 values of
1.43 mg/kg for E toxin, 1.39 mg/kg for crotamine and 0.56 mg/kg for
myotoxin a were determined under these conditions. Lethality was also
observed when either sodium propionate or sodium butyrate was used as a
carrier for E toxin. The effect of these two buffers on crotamine and
myotoxin a was not examined. Injection of E toxin s.c. in water followed
at various time intervals with i.p. injections of 1 M sodium acetate
produced lethality, even when the acetate was injected up to 4 hr after
the toxin challenge.
MH - Acetic Acids/*TOXICITY ; Animal ; Blood/DRUG EFFECTS ; Crotalid Venoms/
*TOXICITY ; Drug Synergism ; Hydrogen-Ion Concentration ; Mice ; Mice,
Inbred C3H ; Support, U.S. Gov't, P.H.S. ; Vehicles/*TOXICITY
SO - Toxicon 1986;24(6):553-8
14
UI - 86304380
AU - Yang SY ; Cuebas D ; Schulz H
TI - 3-Hydroxyacyl-CoA epimerases of rat liver peroxisomes and Escherichia
coli function as auxiliary enzymes in the beta-oxidation of
polyunsaturated fatty acids.
AB - The beta-oxidation of 2-trans,4-cis-decadienoyl-CoA, an assumed
metabolite of linoleic acid, by purified enzymes from mitochondria,
peroxisomes, and Escherichia coli was studied.
2-trans,4-cis-Decadienoyl-CoA is an extremely poor substrate of the
beta-oxidation system reconstituted from mitochondrial enzymes. The
results of a kinetic evaluation lead to the conclusion that in
mitochondria 2-trans,4-cis-decadienoyl-CoA is not directly beta-oxidized,
but instead is reduced by NADPH-dependent 2,4-dienoyl-CoA reductase prior
to its beta-oxidation. Hence, the mitochondrial beta-oxidation of
2-trans,4-cis-decadienoyl-CoA does not require 3-hydroxyacyl-CoA
epimerase, a conclusion which agrees with the finding that
3-hydroxyacyl-CoA epimerase is absent from mitochondria (Chu, C.-H., and
Schulz, H. (1985) FEBS Lett. 185, 129-134). However,
2-trans,4-cis-decadienoyl-CoA can be slowly oxidized by the bifunctional
beta-oxidation enzyme from rat liver peroxisomes, as well as by the fatty
acid oxidation complex from E. coli. The observed rates of
2-trans,4-cis-decadienoyl-CoA degradation by these two multi-functional
proteins were significantly higher than the values calculated according
to steady-state velocity equations derived for coupled enzyme reactions.
This is attributed to the direct transfer of
L-3-hydroxy-4-cis-decenoyl-CoA from the active site of enoyl-CoA
hydratase to that of 3-hydroxyacyl-CoA dehydrogenase on the same protein
molecule. All observations together lead to the suggestion that the chain
shortening of 2-trans,4-cis-decadienoyl-CoA in peroxisomes and in E. coli
occurs simultaneously by two different pathways. The major pathway
involves the NADPH-dependent 2,4-dienoyl-CoA reductase, whereas
3-hydroxyacyl-CoA epimerase functions in the metabolism of
D-3-hydroxyoctanoyl-CoA which is formed via the minor pathway.
MH - Animal ; Cattle ; Epimerases/*METABOLISM ; Escherichia Coli/*ENZYMOLOGY ;
Fatty Acids, Unsaturated/*METABOLISM ; Isomerases/*METABOLISM ; Kinetics
; Liver/*ULTRASTRUCTURE ; Microbodies/*ENZYMOLOGY ; Mitochondria/
ENZYMOLOGY ; Models, Chemical ; Oxidation-Reduction ; Support, Non-U.S.
Gov't ; Support, U.S. Gov't, P.H.S.
SO - J Biol Chem 1986 Sep 15;261(26):12238-43
15
UI - 86299694
AU - Chu TC ; Candia OA ; Iizuka S
TI - Effects of forskolin, prostaglandin F2 alpha, and Ba2+ on the
short-circuit current of the isolated rabbit iris-ciliary body.
AB - To gain information on the role of cyclic AMP (cAMP), ion transport and
cell membrane permeability on aqueous humor formation, agents with
well-known effects on transport properties in other epithelia were tested
on the isolated rabbit iris-ciliary body. Forskolin stimulated the
short-circuit current (SCC) by 37.5% when added to the aqueous-side
solution. Forskolin was ineffective when added to the blood-side solution
or when HCO3- was absent from the bathing solutions. The effect of
forskolin confirms the presence of adenylate cyclase in the ciliary
epithelium and the involvement of cAMP in ion transport. In HCO3- -rich
media, 5 X 10(-5) M prostaglandin F2 alpha (PGF2 alpha), produced a
prompt 25% increase in the SCC when added to the aqueous-side, and a
small stimulatory SCC response when added to the blood-side. No change in
SCC occurred when PGF2 alpha was added to either side of a HCO3- -free
bathing solution. It is implied that cAMP acts on a HCO3- dependent
transport system. These results are consistent with the previously
observed stimulation of the SCC by 8Br-cAMP. BaCl2, 2.5 mM, on the
aqueous-side increased the SCC by 240.5%, but reduced the SCC by 26% when
added to the blood-side solution. The Ba2+ effects indicate the presence
of high conductance K+ channels in the basolateral membranes of both the
pigmented and non-pigmented cell layers.
MH - Animal ; Barium/*PHARMACODYNAMICS ; Ciliary Body/*PHYSIOLOGY ; Electric
Conductivity ; Electrophysiology ; Female ; Forskolin/*PHARMACODYNAMICS ;
In Vitro ; Intraocular Pressure/DRUG EFFECTS ; Iris/*PHYSIOLOGY ;
Prostaglandins F/*PHARMACODYNAMICS ; Rabbits ; Support, U.S. Gov't,
P.H.S.
SO - Curr Eye Res 1986 Jul;5(7):511-6
16
UI - 86260753
AU - Younger EW ; Szabo RM
TI - The stability of prostaglandin E1 in dilute physiological solutions at 37
degrees C.
AB - The stability of prostaglandin E1 (PGE1) in three physiologic solutions
was studied at body temperature (37 degrees C) over 32 days. The
solutions were 100 mcg/ml PGE1 in isotonic saline (pH 4.5), 0.1 M
phosphate buffered water (pH 7.4) or 0.01 M phosphate buffered isotonic
saline (pH 4.7). PGE1 was found to be more stable in the saline and
buffered saline solutions at the pH values of 4.5 and 4.7 respectively.
Twenty-five per cent of the PGE1 remained at 32 days in these solutions
while 95% of the PGE1 in the solution at pH 7.4 was degraded by day 14.
The degradation of PGE1 in the acidic solutions appeared to be nearly
linear when plotted on a semilog graph. This data allows one to use PGE1
in an aqueous, slightly acidic solution in a system that requires it to
be kept at 37 degrees C for up to 30 days such as a biologically
implantable pump. Investigators can use such a system in vivo to study
the effect of known concentrations of PGE1 given over a period of time to
a specific area of interest.
MH - *Alprostadil/ADMINISTRATION & DOSAGE ; Drug Stability ; Hydrogen-Ion
Concentration ; Solutions ; Temperature ; Time Factors
SO - Prostaglandins 1986 May;31(5):923-7
17
UI - 86243274
AU - Cistola DP ; Atkinson D ; Hamilton JA ; Small DM
TI - Phase behavior and bilayer properties of fatty acids: hydrated 1:1
acid-soaps.
AB - The physical properties in water of a series of 1:1 acid-soap compounds
formed from fatty acids and potassium soaps with saturated (10-18
carbons) and omega-9 monounsaturated (18 carbons) hydrocarbon chains have
been studied by using differential scanning calorimetry (DSC), X-ray
diffraction, and direct and polarized light microscopy. DSC showed three
phase transitions corresponding to the melting of crystalline water, the
melting of crystalline lipid hydrocarbon chains, and the decomposition of
the 1:1 acid-soap compound into its parent fatty acid and soap. Low- and
wide-angle X-ray diffraction patterns revealed spacings that corresponded
(with increasing hydration) to acid-soap crystals, hexagonal type II
liquid crystals, and lamellar liquid crystals. The lamellar phase swelled
from bilayer repeat distances of 68 (at 45% H2O) to 303 A (at 90% H2O).
Direct and polarized light micrographs demonstrated the formation of
myelin figures as well as birefringent optical textures corresponding to
hexagonal and lamellar mesophases. Assuming that 1:1 potassium hydrogen
dioleate and water were two components, we constructed a
temperature-composition phase diagram. Interpretation of the data using
the Gibbs phase rule showed that, at greater than 30% water, hydrocarbon
chain melting was accompanied by decomposition of the 1:1 acid-soap
compound and the system changed from a two-component to a three-component
system. Comparison of hydrated 1:1 fatty acid/soap systems with hydrated
soap systems suggests that the reduced degree of charge repulsion between
polar groups causes half-ionized fatty acids in excess water to form
bilayers rather than micelles.(ABSTRACT TRUNCATED AT 250 WORDS)
MH - Calorimetry, Differential Scanning ; Comparative Study ; *Fatty Acids ;
*Lipid Bilayers ; Micelles ; Molecular Conformation ; *Soaps ;
Structure-Activity Relationship ; Support, Non-U.S. Gov't ; Support, U.S.
Gov't, P.H.S. ; *Surface-Active Agents ; X-Ray Diffraction
SO - Biochemistry 1986 May 20;25(10):2804-12
18
UI - 86242252
AU - Meadows J ; Smith RC ; Reeves J
TI - Uric acid protects membranes and linolenic acid from ozone-induced
oxidation.
AB - Aqueous preparations of linolenic acid, bovine serum albumin, and bovine
erythrocyte membrane fragments were bubbled with ozone in the presence or
absence of uric acid. Ozonation of the membrane fragments or the bovine
serum albumin did not result in protein degradation. After 15 min of
ozonation, the absorbance of the thiobarbituric acid-reactive material
increased by 0.34 in the linolenic acid preparation and by 0.08 in the
suspension of membrane fragments. In the presence of uric acid, these
changes in absorbance were reduced to 0.14 for the fatty acid and to 0.01
for the membrane fragments. This result indicates that uric acid protects
lipids from ozone-induced oxidation.
MH - Animal ; Cattle ; Cell-Free System ; Erythrocyte Membrane/*DRUG EFFECTS ;
Free Radicals ; Linolenic Acids/*METABOLISM ; Membrane Lipids/METABOLISM
; Oxidation-Reduction ; *Ozone ; Support, Non-U.S. Gov't ; Support, U.S.
Gov't, Non-P.H.S. ; Uric Acid/*PHARMACODYNAMICS
SO - Biochem Biophys Res Commun 1986 May 29;137(1):536-41
19
UI - 86236444
AU - Merker MP ; Levine L
TI - A protein from the marine mollusc Aplysia californica that is hemolytic
and stimulates arachidonic acid metabolism in cultured mammalian cells.
AB - Aqueous extracts of the foot muscle of the marine mollusc Aplysia
californica contain a proteins(s) that stimulates cytolysis and
prostaglandin production in the C-9 rat liver cell line and hemolysis of
red blood cells. Partial purification of the protein by ion exchange
chromatography and fast protein liquid chromatography resulted in
parallel increases in specific activity for prostaglandin production and
hemolysis. Prostaglandin release occurred both at cytolytic
concentrations of the protein and at lower concentrations that caused no
apparent alterations in cell morphology. Differential sensitivity of a
variety of cell lines to stimulation of prostaglandin production was
observed; one group of cells, including the C-9 rat liver cell line,
displayed a 5-fold stimulation of arachidonic acid metabolism with 1-3
micrograms of a partially purified protein preparation, while a second
group was insensitive to concentrations as high as 20 micrograms protein
of that preparation. Red blood cells also displayed differential
sensitivity to hemolysis: rhesus and squirrel monkey red blood cells were
100-fold more sensitive to lysis by the protein than cebus monkey
erythrocytes. Both activities were abolished by treatment with pepsin,
trypsin or heat and both had a molecular weight of congruent to 45,000,
as determined by gel filtration. Stimulation of both prostaglandin
synthesis and hemolysis was Ca2+ dependent. These observations suggest,
but do not prove, that the protein that causes lysis of red blood cells
and the protein that stimulates arachidonic acid metabolism in the C-9
cell line is the same.
MH - Animal ; Aplysia/*METABOLISM ; Arachidonic Acids/METABOLISM ; Cebus ;
Chromatography, High Pressure Liquid ; Electrophoresis, Polyacrylamide
Gel ; Heat ; Hemolysis/DRUG EFFECTS ; In Vitro ; Liver/METABOLISM ;
Lyngbya Toxins/*ISOLATION & PURIFICATION/PHARMACODYNAMICS ; Macaca
mulatta ; Mice ; Molecular Weight ; Muscles/ANALYSIS ; Prostaglandins/
*BIOSYNTHESIS ; Rabbits ; Rats ; Saimiri ; Species Specificity ; Support,
Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S.
SO - Toxicon 1986;24(5):451-65
20
UI - 86218591
AU - Suzuki Y ; Orii T ; Mori M ; Tatibana M ; Hashimoto T
TI - Deficient activities and proteins of peroxisomal beta-oxidation enzymes
in infants with Zellweger syndrome.
AB - The activities and amounts of enzyme proteins of peroxisomal
beta-oxidation in Japanese children with Zellweger syndrome were
investigated. Cyanide-insensitive fatty acid oxidation, peroxisomal
enoyl-CoA hydratase and 3-oxoacyl-CoA thiolase activities were not
detectable in liver tissue at autopsy, whereas the activities of
mitochondrial enoyl-CoA hydratase, 3-oxoacyl-CoA thiolase and carnitine
palmitoyltransferase were similar to those in the healthy controls. On
immunoblot analysis, immunoreactive proteins of peroxisomal acyl-CoA
oxidase, bifunctional protein and 3-oxoacyl-CoA thiolase were not
detected in the livers, kidneys and fibroblasts from the patients.
Proteins of catalase and some enzymes of mitochondrial fatty acid
oxidation were similar as in normal controls. These data indicate that
increased levels of very-long-chain fatty acids in Zellweger syndrome are
due to the lack of the enzyme proteins of peroxisomal beta-oxidation.
MH - Acetyl CoA Acyltransferase/*DEFICIENCY ; Acyltransferases/*DEFICIENCY ;
Brain Diseases/ENZYMOLOGY ; Electrophoresis, Polyacrylamide Gel ; Enoyl
CoA Hydratases/*DEFICIENCY ; Fatty Acids/*METABOLISM ; Female ; Human ;
Hydro-Lyases/*DEFICIENCY ; Immunologic Technics ; Infant ; Kidney
Diseases/ENZYMOLOGY ; Liver/ENZYMOLOGY ; Liver Diseases/ENZYMOLOGY ; Male
; Microbodies/*ENZYMOLOGY ; Oxidation-Reduction ; Oxidoreductases/
*DEFICIENCY ; Syndrome
SO - Clin Chim Acta 1986 Apr 30;156(2):191-6
21
UI - 86216121
AU - Noy N ; Donnelly TM ; Zakim D
TI - Physical-chemical model for the entry of water-insoluble compounds into
cells. Studies of fatty acid uptake by the liver.
AB - The spontaneous transfer of water-insoluble substances from plasma to the
interior of cells would involve a series of steps in which the substance
of interest dissociates from albumin in plasma, enters the outer half of
the plasma membrane of a cell, crosses the bilayer, and then dissociates
from the inner half of the plasma membrane to enter cell cytosol and
diffuses to sites of its metabolism. We have examined the behavior of
long-chain fatty acids in the uptake process, assuming that none of these
steps is facilitated by the cell during the entry of fatty acids into the
liver. Comparison of the spontaneous rates for each individual step with
rates of uptake of fatty acid by perfused liver leads to the conclusion
that the uptake of fatty acids is not limited by kinetic factors but is
determined instead by the equilibrium distribution (Keq) of fatty acids
between albumin in plasma and the phospholipids of the plasma membrane.
This idea was examined further by determining whether there was a
relationship between the value for Keq and rates of uptake of a fatty
acid and the pattern of kinetics for uptake. The data indicate that there
is a linear relationship between Keq and the rate of uptake, that uptake
rates can be predicted with a high degree of accuracy from thermodynamic
data, and that the pattern of kinetics of uptake is compatible with the
idea that the uptake rate is determined by the relative affinity of a
fatty acid for albumin and membranes.
MH - Animal ; Biological Transport ; Cytosol/METABOLISM ; Fatty Acids,
Nonesterified/*METABOLISM ; Liver/*METABOLISM ; Male ; Mathematics ;
Models, Biological ; Myristic Acids/METABOLISM ; Palmitic Acids/
METABOLISM ; Perfusion ; Rats ; Rats, Inbred Strains ; Solubility ;
Support, U.S. Gov't, P.H.S. ; Water
SO - Biochemistry 1986 Apr 22;25(8):2013-21
22
UI - 86216079
AU - Storch J ; Kleinfeld AM
TI - Transfer of long-chain fluorescent free fatty acids between unilamellar
vesicles.
AB - Movement of free fatty acids (ffa) between small unilamellar vesicles
(SUV) was studied by measuring the transfer of fluorescent
n-(9-anthroyloxy)-labeled analogues (AOffa) between donor and acceptor
vesicles. Donors were composed of egg phosphatidylcholine (PC) loaded
with 1-2 mol % AOffa, and acceptors were egg PC containing 10-12 mol %
N-(7-nitro-2,1,3-benzoxadiazol-4-yl)phosphatidylethanolamine (NBD-PE).
The fluorescence of AO added directly to acceptor SUV was greater than
98% quenched by energy transfer to NBD. Thus, AOffa movement from donor
to acceptor was monitored by the time-dependent decrease in AO
fluorescence. The transfer of the short-chain AOffa, although too fast to
be resolved by the methods used here, is consistent with studies that
find transfer rates on the order of milliseconds and kinetics which are
first order. In contrast, transfer rates for the long-chain AOffa are
more than 2 orders of magnitude slower, and the kinetics of the transfer
process are best described by the sum of two exponentials plus a
constant. The ffa ionization state was also found to be an important
determinant of transfer rate. The charged species transferred an average
of 10-fold faster than the protonated ffa. The ffa pKa in the membrane is
9, as calculated from the pH dependence of transfer. Similar to results
found for other lipids, long-chain AOffa are transferred via water rather
than a collision-mediated process. The aqueous phase route of AOffa
intermembrane transfer is indicated by the lack of effect on transfer of
large alterations in the product of donor and acceptor phospholipid
concentrations. Moreover, the transfer rate is decreased as [NaCl] is
increased from 0.1 to 4 M. This effect of ionic strength is probably due
not only to a decrease in the aqueous phase partition of the AOffa but
also to an alteration in bilayer structure, as measured by fluorescence
polarization of 1,6-diphenyl-1,3,5-hexatriene. The observed kinetics are
consistent with a model in which the transfer involves two steps:
transbilayer movement between the inner and outer bilayer leaflets,
followed by transfer from the outer leaflet to the aqueous phase (off
rate). Within the framework of this model, the observed slow rate is
primarily determined by the rate of transbilayer movement, and the
observed fast rate is approximately equal to the off rate. The off rate
is about 10-fold faster than the rate of transbilayer movement.
MH - Comparative Study ; *Fatty Acids, Nonesterified ; Fluoresceins ;
Fluorescent Dyes ; Hydrogen-Ion Concentration ; Kinetics ; *Liposomes ;
Mathematics ; Models, Biological ; Osmolar Concentration ;
*Phosphatidylcholines ; Spectrometry, Fluorescence ; Structure-Activity
Relationship ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, Non-P.H.S.
SO - Biochemistry 1986 Apr 8;25(7):1717-26
23
UI - 86212652
AU - Sato M ; Dunn MJ
TI - Osmolality, vasopressin-stimulated cAMP, and PGE2 synthesis in rat
collecting tubule cells.
AB - Using rat renal papillary collecting tubule (RPCT) cells in culture, we
examined the interactions of extracellular osmolality,
vasopressin-stimulated cAMP, and prostaglandin E2 (PGE2) synthesis.
Hypertonic solutions composed of equiosmolar amounts of urea and sodium
chloride, 900-2,400 mosM, potentiated the increases of intracellular cAMP
after vasopressin stimulation. Sodium chloride, rather than urea, was the
important solute. The mechanism of this augmented cAMP response was
complex, probably involving increased synthesis, decreased degradation,
and reduced efflux of cAMP from the RPCT cells. The potentiating actions
of hypertonic sodium chloride were specific for vasopressin-stimulated
cAMP and were not observed for forskolin or PGE2-stimulated cAMP.
Hypertonic solutions inhibited RPCT cell PGE2 production, and sodium
chloride, rather than urea, was again the important solute. The enzymatic
site of sodium chloride inhibition of PGE2 synthesis was apparently on
the phospholipase enzymes, assessed by calcium ionophore and bradykinin
stimulation, and not on cyclooxygenase, measured by arachidonic acid
responsiveness. Reductions of osmolality, from 1,800 to 300 mosM, acutely
increased PGE2 release, possibly through a calcium-dependent stimulation
of phospholipase. We conclude that conditions that prevail in vivo during
antidiuresis, namely hypertonicity of the papillary interstitium, may
augment vasopressin responsiveness through increments of collecting
tubule cAMP and reductions of PGE2 which could, in concert, maximize
water reabsorption in the collecting tubule.
MH - A-23187/PHARMACODYNAMICS ; Adenosine Cyclic Monophosphate/*BIOSYNTHESIS ;
Adenyl Cyclase/METABOLISM ; Animal ; Arachidonic Acids/PHARMACODYNAMICS ;
Argipressin/*PHARMACODYNAMICS ; Forskolin/PHARMACODYNAMICS ; Kidney
Tubules/*METABOLISM ; Kidney Tubules, Collecting/CYTOLOGY/ENZYMOLOGY/
*METABOLISM ; Osmolar Concentration ; Phosphodiesterase Inhibitors/
PHARMACODYNAMICS ; Prostaglandins E/*BIOSYNTHESIS/PHARMACODYNAMICS ; Rats
; Rats, Inbred Strains ; Sodium Chloride/PHARMACODYNAMICS ; Stimulation,
Chemical ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. ; Urea/
PHARMACODYNAMICS ; 1-Methyl-3-Isobutylxanthine/PHARMACODYNAMICS
SO - Am J Physiol 1986 May;250(5 Pt 2):F802-10
24
UI - 86211288
AU - Bojesen E ; Bojesen IN
TI - The influence of renal papillary urea concentrations and of plasma
vasopressin on the urinary prostaglandins E2 and F2 alpha excretion in
conscious rats in steady state of urine formation.
AB - Urinary excretion rates of PGE2 and PGF2 alpha were measured
radioimmunologically in four different groups of unanaesthetized rats:
water diuretic rats (I), rats with free access to water (II), water
deprived rats (III) and 1.5% saline-loaded rats (IV). The animals were
decapitated when steady states of urine formation were ascertained for
three to six spontaneously delivered urine portions. Plasma vasopressin
was measured radioimmunologically and urea, sodium, potassium
concentrations and osmolalities of papillary fluids and of bladder urines
were determined. Group means of urinary prostaglandin excretion,
papillary urea concentration and logarithmic-transformed plasma
vasopressin values vary in parallel for three of the groups (I, II and
III) but a dissociation of the effects of papillary urea and vasopressin
on the prostaglandin excretion was obtained for group IV. Statistical
analyses indicated that the differences in prostaglandin excretion rates
between group I and the three other groups are accounted for by the
combined effects of vasopressin and papillary urea. The results support
the hypothesis that vasopressin stimulates release of arachidonic acid in
the papilla and that urea inhibits the trapping of this prostaglandin
precursor in cellular lipids. The ratio of urinary PGF2 alpha to PGE2
varied greatly between groups but no consistent dependency on the
measured parameters was found.
MH - Animal ; Diuresis/DRUG EFFECTS ; Kidney Medulla/*ANALYSIS ; Osmolar
Concentration ; Potassium/ANALYSIS ; Prostaglandins E/*URINE ;
Prostaglandins F/*URINE ; Rats ; Rats, Inbred Strains ; Sodium/ANALYSIS ;
Sodium Chloride/PHARMACODYNAMICS ; Urea/*ANALYSIS ; Urine ; Vasopressins/
*BLOOD
SO - Acta Physiol Scand 1986 Feb;126(2):279-88
25
UI - 86187861
AU - Blatt E ; Corin AF
TI - The microsecond rotational motions of eosin-labelled fatty acids in
multilamellar vesicles.
AB - The rotational properties of two eosin-labelled fatty acids of different
alkyl chain length have been studied in large multilamellar
dimyristoylphosphatidylcholine vesicles. The location of the probes at
the surface region were ascertained by quenching experiments using a
hydrophilic divalent cation solubilized in the aqueous phase (Cu2+) and a
hydrophobic aromatic aniline (N,N-dimethylaniline) associated with the
lipid. Phosphorescence anisotropy measurements reveal that above the
phospholipid phase transition the polarization of eosin luminescence
decays monoexponentially in the micro-to-millisecond time range, while
below the phase transition a biexponential decay is observed. A model is
proposed which attributes the time constants to two separate motions,
discrete jumps or 'flipping' of the eosin moiety within restricted
boundaries and long-axis rotation. The value of the time-independent term
changes with probe position and temperature and reflects orientational
constraints imposed by lipid-chromophore interactions. The implications
of these results for the study of protein rotations in membranes are
discussed.
MH - Comparative Study ; Dimyristoylphosphatidylcholine ; *Eosin ; *Fatty
Acids, Nonesterified ; *Liposomes ; Luminescence ; Models, Biological ;
Structure-Activity Relationship ; Support, Non-U.S. Gov't ;
Thermodynamics
SO - Biochim Biophys Acta 1986 May 9;857(1):85-94
26
UI - 86184158
AU - Hollander D ; Gerard EM ; Boyd CA
TI - Transport of butyric acid in vascularly perfused anuran small intestine:
importance of pH and anion transport.
AB - Butyric acid transport was studied in the isolated, vascularly perfused
frog small intestine. At luminal butyric acid concentrations of 5-50 mM,
absorption was a nonlinear function of the luminal concentration, whereas
the relationship of absorption to concentration remained linear at
0-1,000 microM. The most important factor regulating the rate and
direction of butyric acid transport was the pH. We used unidirectional
flux analysis to determine net transport across the epithelium while the
pH of the luminal or vascular compartments was changed. We found a four-
to fivefold decrease in butyric acid transport into the portal
circulation as the lumen pH was increased from 6.0 to 8.0. The pH of the
vascular perfusate influenced the vascular-to-lumen transport of butyric
acid in the same proportions. The second important regulatory factor of
butyric acid transport was the
4,4'-diisothiocyananostilbene-2,2'-disulfonic acid (DIDS)-sensitive anion
transport protein. DIDS added to the lumen at 10(-6) M decreased butyric
acid transport by approximately 40% at pH 7.4. DIDS also inhibited
butyric acid transport when added to the vascular perfusate or when
transport was measured in a vascular-to-lumen direction. We suggest that,
at the relatively low pH of the proximal small intestine, butyric acid
becomes protonated and lipophilic and is mainly transported directly
through the cell membrane. At the more alkaline pH of the distal small
intestine butyric acid is in the ionized form and transport by the
DIDS-sensitive anion transport protein may predominate.
MH - Acetazolamide/PHARMACODYNAMICS ; Amiloride/PHARMACODYNAMICS ; Animal ;
Anions/*METABOLISM ; Biological Transport ; Butyrates/*METABOLISM ;
Butyric Acids/*METABOLISM ; *Hydrogen-Ion Concentration ; Intestine,
Small/*METABOLISM ; Kinetics ; Methylglucosides/METABOLISM ; Perfusion ;
Probenecid/PHARMACODYNAMICS ; Rana Esculenta ; Support, Non-U.S. Gov't ;
Support, U.S. Gov't, P.H.S. ; SITS/ANALOGS & DERIVATIVES/PHARMACODYNAMICS
SO - Am J Physiol 1986 Apr;250(4 Pt 1):G469-74
27
UI - 86178050
AU - Kasser TR ; Martin RJ
TI - Induction of ventrolateral hypothalamic fatty acid oxidation in diabetic
rats.
AB - Diabetic rats were used to test a previous hypothesis that alterations in
ventrolateral hypothalamic (VLH) fatty acid oxidation observed in over-
and underfed rats were a function of the animals' peripheral energy
balance and not merely a function of their energy intake. Standard
adaptations to the diabetic condition were exhibited in streptozotocin
diabetic rats such as depressed body weights, hyperphagia and
hyperglycemia, elevated serum free fatty acids, depressed insulin
concentrations, depressed hepatic glucose oxidation and elevated hepatic
fatty acid oxidation. Rates of VLH fatty acid oxidation to CO2 and to an
acid, water-soluble fraction in diabetic rats were elevated relative to
non-diabetic rats. The alterations in VLH fatty acid oxidation in
diabetic rats were similar to changes previously observed in animals
exhibiting a negative energy balance. The results were discussed with
respect to the concept that VLH fatty acid oxidation was a component in
the recognition of peripheral energy balance and, in part, served to
alter the regulators of energy balance and food intake.
MH - Animal ; Diabetes Mellitus, Experimental/*METABOLISM ; Eating ; Energy
Metabolism ; Hypothalamic Area, Lateral/*METABOLISM ; Hypothalamus,
Middle/METABOLISM ; Liver/METABOLISM ; Male ; Oxidation-Reduction ;
Palmitates/*METABOLISM ; Palmitic Acids/*METABOLISM ; Rats ; Rats, Zucker
; Streptozotocin
SO - Physiol Behav 1986;36(2):385-8
28
UI - 86162769
AU - Haylor J ; Lote CJ ; Thewles A
TI - The effect of sodium bicarbonate on the flow-dependency of urinary
prostaglandin excretion in man.
AB - The influence of oral water loading on the excretion rate of
prostaglandin (PG) E was investigated in healthy human subjects in a
control study where the urine was acidic (pH 5.7) and after oral sodium
bicarbonate, which made the urine mildly alkaline (pH 7.2). PGE was
immediately extracted from urine and measured by a radioimmunoassay
technique. After sodium bicarbonate (5 g) the urinary PGE excretion rate
was some three-fold higher (P less than 0.01) than in the control study,
in the absence of any significant difference in the urine flow
(approximately 80 ml/h). In the control study (urine pH 5.7) the urinary
PGE excretion rate increased significantly (P less than 0.01) as the
urine flow rose in response to the oral fluid load. However, after sodium
bicarbonate, PGE excretion did not alter after the fluid load despite a
10-fold increase in urine flow. Since after bicarbonate administration
PGE excretion is independent of urine flow, mildly alkaline urine may
represent a condition under which renal PGE synthesis can be effectively
assessed from measurements of urinary PGE excretion, in the presence of
changes in urine flow. In addition, the results are compatible with the
hypothesis that, in man, PGE may be passively reabsorbed in the distal
nephron, and a reduction in this reabsorption could contribute to or be
responsible for the dependency of the excretion rate of PGE on urine
flow.
MH - Adult ; Bicarbonates/*PHARMACODYNAMICS ; *Diuresis ; Human ; Hydrogen-Ion
Concentration ; Male ; Osmolar Concentration ; Prostaglandins E/*URINE ;
Sodium/*PHARMACODYNAMICS
SO - Clin Sci 1986 Feb;70(2):141-5
29
UI - 86160591
AU - Berry CN ; Griffiths RJ ; Hoult JR ; Moore PK ; Taylor GW
TI - Identification of 6-oxo-prostaglandin E1 as a naturally occurring
prostanoid generated by rat lung.
AB - The spontaneous release of prostanoids from rat isolated perfused lungs
was studied after acid/organic extraction of perfusates by bioassay,
radioimmunoassay, thin layer and high performance liquid chromatographic
methods and by gas chromatography-negative ion mass spectroscopy
(g.c.n.i.m.s.). An acid/organic extractable anti-aggregatory vasodilator
prostaglandin which inhibited the twitch response of the field-stimulated
guinea-pig vas deferens was released from the Krebs-perfused rat lung in
nanogram amounts similar to those of other detected prostanoids. Parallel
biological assay suggested that this prostaglandin had very closely
similar pharmacological activity to authentic 6-oxo-prostaglandin E1
(6-oxo-PGE1), a metabolite of prostacyclin (PGI2) generated by the action
of the enzyme 9-hydroxyprostaglandin dehydrogenase (9-PGDH). 6-oxo-PGE1
was identified conclusively in extracts of rat lung perfusate by thin
layer chromatography, high performance liquid chromatography and
g.c./m.s. combined with bioassay (inhibition of platelet aggregation),
and its covalent structure was defined by g.c. negative ion chemical
ionization mass spectroscopy. The rank order of spontaneous release of
prostanoids (measured by radioimmunoassay) from the perfused rat lung was
6-oxo-PGF1 alpha greater than thromboxane B2 (TXB2) greater than PGE2
greater than 6-oxo-PGE1 (measured biologically) greater than PGF2 alpha.
Release of all five prostanoids was inhibited by indomethacin, but only
that of 6-oxo-PGE1 was inhibited by naringenin. Rat lung 100,000 g
cytosolic supernatants contained 9-PGDH activity capable of removing 9
beta-tritium from labelled prostacyclin and forming an acid/organic
extractable 6-oxo-PGE1-like anti-aggregatory substance. This 9-PGDH
activity was inhibited by naringenin (IC50 10.3 microM).(ABSTRACT
TRUNCATED AT 250 WORDS)
MH - Alprostadil/*ANALOGS & DERIVATIVES/ANALYSIS/BIOSYNTHESIS ; Animal ;
Chromatography, High Pressure Liquid ; Chromatography, Thin Layer ;
Cytosol/ENZYMOLOGY ; Flavones/PHARMACODYNAMICS ; Hydrogen-Ion
Concentration ; Hydroxyprostaglandin Dehydrogenases/ANTAGONISTS &
INHIBITORS/METABOLISM ; In Vitro ; Lung/ENZYMOLOGY/*METABOLISM ; Male ;
Mass Fragmentography ; Perfusion ; Prostaglandins/ANALYSIS/*BIOSYNTHESIS
; Radioimmunoassay ; Rats ; Rats, Inbred Strains ; Support, Non-U.S.
Gov't
SO - Br J Pharmacol 1986 Feb;87(2):327-35
30
UI - 86094356
AU - Hamilton JA ; Cistola DP
TI - Transfer of oleic acid between albumin and phospholipid vesicles.
AB - The net transfer of oleic acid between egg phosphatidylcholine
unilamellar vesicles and bovine serum albumin has been monitored by 13C
NMR spectroscopy and 90% isotopically substituted [1-13C]oleic acid. The
carboxyl chemical shifts of oleic acid bound to albumin were different
from those for oleic acid in phospholipid vesicles. Therefore, in
mixtures of donor particles (vesicles or albumin with oleic acid) and
acceptor particles (fatty acid-free albumin or vesicles), the equilibrium
distribution of oleic acid was determined from chemical shift and peak
intensity data without separation of donor and acceptor particles. In a
system containing equal masses of albumin and phospholipid and a
stoichiometry of 4-5 mol of oleic acid per mol of albumin, the oleic acid
distribution was pH dependent, with greater than or equal to 80% of the
oleic acid associated with albumin at pH 7.4; association was greater
than or equal to 90% at pH 8.0. Decreasing the pH below 7.4 markedly
decreased the proportion of fatty acid bound to albumin; at pH 5.4, less
than or equal to 10% of the oleic acid was bound to albumin and greater
than 90% was associated with vesicles. The distribution was reversible
with pH and was independent of whether vesicles or albumin acted as a
donor. These data suggest that pH may strongly influence the partitioning
of fatty acid between cellular membranes and albumin. The 13C NMR method
is also advantageous because it provides information about the structural
environments of oleic acid bound to albumin or phospholipid, the
ionization state of oleic acid in each environment, and the structural
integrity of the vesicles. In addition, minimum and maximum limits for
the exchange rates of oleic acid among different environments were
obtained from the NMR data.
MH - Fatty Acids/METABOLISM ; Hydrogen-Ion Concentration ; Liposomes/
*METABOLISM ; Nuclear Magnetic Resonance ; Oleic Acids/*METABOLISM ;
Phosphatidylcholines/*METABOLISM ; Serum Albumin, Bovine/*METABOLISM ;
Support, U.S. Gov't, P.H.S.
SO - Proc Natl Acad Sci USA 1986 Jan;83(1):82-6