The phorbol ester TPA prevents the expression of both glucagon desensitisation and the glucagon‐mediated block of insulin stimulation of the peripheral plasma membrane cyclic AMP phosphodiesterase in rat hepatocytes

FEBS Letters

Gawler, Debra J.¹  Heyworth, Clare M.²  Wilson, Sally P.²  Houslay, Miles D.¹ 

[1] Department of Biochemistry & Applied Molecular Biology, UMIST, PO Box 88, Manchester M60 1QD, England;Institute of Biochemistry, University of Glasgow, Glasgow G12 8QQ, Scotland

关键词: Glucagon;    Tumor promotor;    Adenylate cyclase;    Phorbol ester;    Desensitisation;    Cyclic AMP phosphodiesterase;   

DOI  :  10.1016/0014-5793(85)81241-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The phorbol ester TPA (12-O-tetradecanoyl phorbol-13-acetate) causes a dose-dependent inhibition of the glucagon-stimulated adenylate cyclase activity expressed in plasma membranes isolated from TPA-treated hypatocytes. However, no observable inhibitory effect of TPA on adenylate cyclase activity was observed in cells which had been exposed to glucagon for 5 min, prior to isolation, to desensitise adenylate cyclase. The degree of inhibition of adenylate cyclase elicited by both glucagon desensitisation and TPA treatment of hepatocytes was identical. Pre-treatment of hepatocytes with TPA was also found to prevent glucagon from blocking insulin's activation of the peripheral plasma membrane cyclic AMP phosphodiesterase in intact hepatocytes. TPA treatment also inhibited the ability of cholera toxin to activate the peripheral cyclic AMP phosphodiesterase in intact hepatocytes. It is suggested that in these particular instances TPA and glucagon elicit mutually exclusive processes rather than TPA mimicking glucagon desensitisation per se.

【 授权许可】

Unknown