Structural specificity for prostaglandin effects on hepatocyte glycogenolysis.
Prostaglandins (PGs) are known to have effects on hepatic glucose metabolism. Some actions of PGs in intact liver systems may not involve PG effects directly at the level of the hepatocyte. To define the ability of structurally distinct prostaglandins to affect hepatocyte metabolism directly, the regulation of glycogenolysis was studied in hepatocytes isolated from male Sprague-Dawley rats. PGF and PGB2 inhibited glucagon-stimulated glycogenolysis in the hepatocyte system. Pinane thromboxane A2 (PTA2) and PGD2 had no effect on glucagon-stimulated glycogenolysis. Consistent with their inhibition of glucagon-stimulated glycogenolysis, PGF2 and PGF2 alpha inhibited glucagon-stimulated hepatocyte cyclic AMP accumulation. These actions of PGB2 and PGF2 alpha are identical with those previously reported for PGE2. Additionally, PGE2, PGF2 alpha and PGB2 inhibited glucagon-stimulated adenylate cyclase activity in purified hepatic plasma membranes. In contrast, PGF2 alpha, PGD2 and PTA2 were all without affect on basal rates of hepatocyte glycogenolysis or hepatocyte cyclic AMP content. PGE2 also inhibited glycogenolysis stimulated by the alpha-adrenergic agonist phenylephrine. Exogenous arachidonic acid was not able to reproduce the affects of PGE2 or PGF2 alpha on hepatocyte glycogenolysis, consistent with an extra-hepatocyte source of the prostaglandins in the intact liver. Thus PGE2 and PGF2 alpha act specifically to inhibit glucagon-stimulated adenylate cyclase activity. No prostaglandin tested was found to stimulate glycogenolysis. PGE2 and PGF2 alpha may represent intra-hepatic modulators of hepatocyte glucose metabolism.
Brass
E P
EP
Department of Medicine, Case Western Reserve University, Cleveland, OH 44106.
Garrity
M J
MJ
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D011456:Prostaglandins B / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013928:Thromboxane A2 / Q000494:pharmacology
D011453:Prostaglandins; D011456:Prostaglandins B; D010656:Phenylephrine; D013928:Thromboxane A2; D006003:Glycogen; D005934:Glucagon; D015237:Dinoprost; C042026:prostaglandin B2; D000242:Cyclic AMP; D015232:Dinoprostone; D015230:Prostaglandin D2