Mechanisms for the emergence of catecholamine-sensitive adenylate cyclase and β-adrenergic receptors in cultured hepatocytes: Dependence on protein and RNA synthesis and suppression by isoproterenol

Abstract

Adult male rat hepatocytes, which normally respond poorly to β-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 β-adrenoceptor ligand [ 125I]cyanopindolol. The emergence of β-adrenergic responsiveness did not require cell attachment or serum. Addition of dexamethasone, insulin, thyroxine or dihydortestosterone to the cultures, singly or in combination, did not prevent the augmented β-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 β-adrenoceptor binding.