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

• Published in: FEBS letters 1983-12, Vol.164 (2), p.291-298
• Main Authors: Refsnes, M., Sandnes, D., Melien, Ø., Sand, T.E., Jacobsen, S., Christoffersen, T.
• Format: Article
• Language: English
• Subjects: Actinomycin D; Adenylate cyclase; Adenylyl Cyclases - metabolism; Animals; beta -adrenergic; Biological and medical sciences; Cell physiology; Cells, Cultured; cyanopindolol; Cycloheximide; Cycloheximide - pharmacology; Dactinomycin - pharmacology; Dexamethasone - pharmacology; Fundamental and applied biological sciences. Psychology; hepatocytes; Insulin - pharmacology; Isoproterenol - pharmacology; Liver - metabolism; Male; Molecular and cellular biology; Neurotransmission; Primary culture; Protein Biosynthesis - drug effects; Rat hepatocyte; Rats; Receptors, Adrenergic, beta - metabolism; RNA - biosynthesis; Testosterone - pharmacology; Thyroxine - pharmacology; β-Adrenergic receptor
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(83)80304-4

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.