Mechanisms for the emergence of catecholamine-sensitive adenylate cyclase and beta-adrenergic receptors in cultured hepatocytes. Dependence on protein and RNA synthesis and suppression by isoproterenol.
Adult male rat hepatocytes, which normally respond poorly to beta-adrenergic agents, acquire such responsiveness during primary monolayer culture. We here show that the rise in catecholamine-sensitive adenylate cyclase activity in hepatocytes in vitro is closely paralleled by an increase in the ability to bind the beta-adrenoceptor ligand [125I]cyanopindolol. The emergence of beta-adrenergic responsiveness did not require cell attachment or serum. Addition of dexamethasone, insulin, thyroxine or dihydrotestosterone to the cultures, singly or in combination, did not prevent the augmented beta-adrenergic responsiveness. The increase in catecholamine-sensitive adenylate cyclase activity and [125I]cyanopindolol binding could be blocked by cycloheximide or actinomycin D. Exposure of the cultures to isoproterenol at 3-hourly intervals led to a dose-dependent suppression of the rise in isoproterenol-responsive adenylate cyclase and prevented the increase in beta-adrenoceptor binding.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D014176:Protein Biosynthesis / Q000187:drug effects; D012313:RNA / Q000096:biosynthesis*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology; D013974:Thyroxine / Q000494:pharmacology
D007328:Insulin; D011943:Receptors, Adrenergic, beta; D003609:Dactinomycin; D013739:Testosterone; D012313:RNA; D003907:Dexamethasone; D003513:Cycloheximide; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D013974:Thyroxine