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Biomedical subjects

R R Gorman

Publications and source records attributed to R R Gorman.

102 records · Page 6Linked to original sources
PubMed1976

The chemical structure of prostaglandin X (prostacyclin).

The chemical structure of prostaglandin X, the anti-aggregatory substance derived from prostaglandin endoperoxides, is 9-deoxy-6, 6alpha-epoxy-delta5-PGF1alpha. The stable compound formed when prostaglandin X undergoes a chemical transformation in biological systems in 6-keto-PGF1alpha. Prostaglandin X is stabilized in aqueous preparations by raising the pH to 8.5 or higher. The trivial name prostacyclin is proposed for 9-deoxy-6, 9alpha-epoxy-delta5-PGF1alpha.

Animals↗
PubMed1976

Modulation of platelet cyclic nucleotide content by PGE1 and the prostaglandin endoperoxide PGG2.

The effects of prostaglandin E1 and prostaglandin G2, the prostaglandin endoperoxide, on platelet cyclic nucleotide concentrations were measured in platelet rich plasma (PRP), and in washed intact platelets. PGE1 was found to be a potent stimulator of platelet cAMP levels in both PRP and washed cells, and to inhibit aggregation in both systems. PGE1 did not change platelet cGMP levels in either PRP or washed cells. PGG2 which is a potent inducer of platelet aggregation, did not affect either the basal cAMP or the basal cGMP concentration. However, PGG2 was found to antagonize the increases in cAMP content in response to PGE1 in both PRP and washed platelets. The addition to our system of a cyclic nucleotide phosphodiesterase inhbitor, theophylline, did not change our findings. It is suggested that PGG2 may induce platelet aggregation by inhibiting PGE1-stimulated cAMP accumulation.

Blood Platelets↗
PubMed1975

Inhibition of basal and hormone-stimulated adenylate cyclase in adipocyte ghosts by the prostaglandin endoperoxide prostaglandin H2.

The prostaglandin endoperoxide PGH2 (15-hydroxy-9alpha, 11alpha-peroxidoprosta-5,13-dienoic acid), at a concentration of 2.8 x 10(-5) M inhibited basal adenylate cyclase activity 11% and epinephrine-stimulated activity 30 to 35%. PGH2 inhibited epinephrine-stimulated enzyme activity in the presence of 10 mM theophylline, 2.5 mM adenosine 3':5'-monophosphate (cAMP), or in the absence of inhibitors or substrates of the cAMP phosphodiesterase. When the cAMP phosphodiesterase was assayed directly using 62 nM and 1.1 muM cAMP, PGH2 did not affect the 100,000 x g particulate cAMP phosphodiesterase from fat cells. The inhibition of adenylate cyclase by PGH2 was readily reversible. A 6-min preincubation of ghost membranes with PGH2, followed by washing, did not alter subsequent epinephrine-stimulated adenylate cyclase activity. During epinephrine stimulation, the PGH2 inhibition was apparent on initial rates of cAMP synthesis, and the addition of PGH2 to the enzyme system at any point during an assay markedly reduced the rate of cAMP synthesis. Between 2.8 x 10(-7) M and 2.8 x 10(-5) M, PGH2 inhibited epinephrine-stimulated enzyme activity in a concentration-dependent manner. The stimulation of adenylate cyclase by thyroid-stimulating hormone, glucagon, and adrenocorticotropic hormone as well as by epinephrine was antagonized by PGH2, suggesting that PGH2 may be an endogenous feedback regulator of hormone-stimulated lipolysis in adipose tissue.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1975

Prostaglandin d2 as a potential antithrombotic agent.

Prostaglandin D2 was found to be a potent inhibitor of platelet aggregation. Aggregation of human platelets by ADP, collagen and prostaglandin G2 was inhibited more strongly by PGD2 than by PGE1. Although ADP-induced aggregation of rabbit platelets was inhibited more strongly by PGE1 than by PGD2 the latter prostaglandin gave a more long-lasting inhibitory effect on platelet aggregation following intravenous or oral administration. These results coupled with the finding that PGD2 has less hypotensive effects on the cardiovascular system than PGE1 suggest the possible use of PGD2 as an antithrombotic agent.

Adenosine Diphosphate↗
PubMed1973

Epinephrine binding and the selective restoration of adenylate cyclase activity in fat-fed rats.

Fat feeding results in a progressive loss of epineph-rine- and glucagon-stimulated adenylate cyclase activity in adipocyte plasma membrane sacs (ghosts). Basal and NaF-stimulated adenylate cyclase activities in fat-fed animals are not significantly different from those in preparations obtained from chow-fed rats. The high fat diet increases the mean adipocyte diameter rapidly, but increased cell size, at least in the case of epinephrine stimulation, is not responsible for the decreased hormone-stimulated adenylate cyclase activity. Diet shifts to high carbohydrate or high protein regimens result in the restoration of the epinephrine-stimulated, but not the glucagon-stimulated, activity without a significant reduction in mean cell diameter. Both hormone-resistant adipocyte ghosts from fat-fed animals and ghosts obtained from hormone-sensitive adipocytes bind the same amount of [(3)H]epinephrine per milligram of membrane protein. These data indicate that the fat diet inhibits epinephrine-stimulated adenylate cyclase activity at a point between the hormone receptor and the catalytic unit of adenylate cyclase.

Adenylyl Cyclases↗
PubMed1972

Effects of starvation, refeeding, and fat feeding on adipocyte ghost adenyl cyclase activity.

Basal adenyl cyclase activity and its response to epinephrine and glucagon were studied in isolated adipocyte ghosts obtained from fed, starved, refed, and fat-diet-adapted rats. Epinephrine stimulation of adenyl cyclase was significantly increased in fasted rats, but the glucagon response did not change. Rats fasted for 48 hr and refed a high carbohydrate, low fat diet for 48 or 96 hr showed no differences from chow-fed animals in either basal or hormone-stimulated adenyl cyclase activity. Rats adapted to a high fat, low carbohydrate diet showed an initial and transitory increase in basal activity but a progressive loss of epinephrine- and glucagon-stimulated enzyme activities. The loss in hormone responsiveness correlated well with a decrease in hormone-stimulated lipolysis of fat pads and was associated with a significant increase in fat cell diameter.

Adenosine Triphosphate↗
PubMed1971

Biochemical adaptation of rat liver in response to marginal oxygen toxicity.

1. Hepatic glucose 6-phosphate dehydrogenase activity was increased in rats exposed to 5lb/in(2) (equivalent to 27000ft), 100% O(2) when compared with control animals in a 14.7lb/in(2) (sea level), air environment. Glyceraldehyde 3-phosphate dehydrogenase, isocitrate dehydrogenase, and succinate dehydrogenase were not affected by the 5lb/in(2), 100% O(2) environment. 2. Animals exposed to the hyperoxic environment consumed food, expired CO(2) and gained weight at the same rate as normoxic control animals. Additionally, blood glucose and liver glycogen concentrations were unchanged in the hyperoxic animals. The only readily apparent physiological difference in the hyperoxic animals was a decreased haematocrit. 3. The increase in glucose 6-phosphate dehydrogenase was eliminated by the injection of actinomycin D or cycloheximide. 4. Expiration of (14)CO(2) from [1-(14)C]glucose was approximately the same in hyperoxic and normoxic rats. However, (14)CO(2) expiration from [6-(14)C]glucose was markedly decreased in the animals exposed to the hyperoxic environment. 5. Calculations of the relative importance of the pentose phosphate pathway versus the tricarboxylic acid cycle plus glycolysis indicated that the livers from animals in the 5lb/in(2), 100% O(2) environment metabolized twice as much carbohydrate by way of the pentose phosphate pathway as did those from the sea-level air control animals. 6. In livers of rats exposed to 5lb/in(2), 100% O(2) the concentrations of pyruvate, citrate and 2-oxoglutarate were increased, that of isocitrate was slightly elevated, whereas the concentrations of succinate, fumarate and malate were decreased. 7. An inactivation of both tricarboxylic acid cycle lipoate-containing dehydrogenases, pyruvate and 2-oxoglutarate, under hyperoxic conditions is proposed. 8. The adaptive significance of the induction of glucose 6-phosphate dehydrogenase and the resultant production of NADPH under hyperoxic conditions is discussed.

Adaptation, Physiological↗