Effect of prostaglandins and their analogues on hormone-stimulated glycogenolysis in primary cultures of rat hepatocytes.
Hepatocytes were isolated by collagenase perfusion method from adult male rats, cultured and then prelabeled with [14C]glucose. The [14C]glycogen-labeled cells were used in experiments for effect of prostaglandins on hormone-stimulated glycogenolysis. Prostaglandin E1, prostaglandin E2 and 16,16-dimethylprostaglandin E2, but not prostaglandin D2 or prostaglandin F2 alpha, inhibited glycogenolysis stimulated by glucagon, epinephrine, isoproterenol (beta-adrenergic agonist) or epinephrine in the presence of propranolol (beta-antagonist) in primary cultured hepatocytes. The inhibitory effects on day 2 of cultures were approx. twice those on day 1. Dimethylprostaglandin E2 (10(-6)M) caused 60-70% inhibitions of the stimulations by these substances. In the case of the stimulation by glucagon, the inhibition further increased by 80-100% on day 3 of culture. Prostaglandin E1 and prostaglandin E2 caused less inhibition than dimethylprostaglandin E2 of all these stimulations. Dinorprostaglandin E1 (9 alpha,13-dihydroxy-7-ketodinorprost-11-enoic acid), which is a hepatocyte-metabolite of prostaglandin E1 and prostaglandin E2, and arachidonic acid did not have any inhibitory effects. These data indicate that the E series of prostaglandins may function as the regulation of hepatic glycogenolysis stimulated by epinephrine and glucagon, and that their rapid degradation system may contribute to the modulation of the action in liver.
Department of Medical Chemistry, Kansai Medical School, Osaka, Japan.
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D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone; D004837:Epinephrine / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D008112:Liver Glycogen; D011453:Prostaglandins; D011458:Prostaglandins E; D005934:Glucagon; D011433:Propranolol; D000527:Alprostadil; D005947:Glucose; D015232:Dinoprostone; D007545:Isoproterenol; D015064:16,16-Dimethylprostaglandin E2; D004837:Epinephrine