The phorbol ester, TPA inhibits glucagon‐stimulated adenylate cyclase activity

FEBS Letters

Heyworth, Clare M.²  Kinsella, Anne R.¹  Houslay, Miles D.²  Whetton, Anthony D.¹ 

[1] Paterson Laboratories, Christie Hospital and Holt Radium Institute, Manchester M20 9BX, England;Department of Biochemistry and Applied Molecular Biology, University of Manchester Institute of Science and Technology, PO Box 88, Manchester M60 1QD, England

关键词: Protein kinase C;    Guanine nucleotide regulation;    Tumor promoter;    Adenylate cyclase;    Phorbol ester;    Calcium;   

DOI  :  10.1016/0014-5793(84)81364-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The ability of glucagon (10 nM) to increase hepatocyte intracellular cyclic AMP concentrations was reduced markedly by the tumour-promoting phorbol ester TPA (12-O-tetradecanoyl phorbol-13-acetate). The half-maximal inhibitory effect occurred at 0.14 ng/ml TPA. This action occurred in the presence of the cyclic AMP phosphodiesterase inhibitor isobutylmethylxanthine (1 mM) indicating that TPA inhibited glucagon-stimulated adenylate cyclase activity. TPA did not affect either the binding of glucagon to its receptor or ATP concentrations within the cell. TPA did inhibit the increase in intracellular cyclic AMP initiated by the action of cholera toxin (1 μg/ml) under conditions where phosphodiesterase activity was blocked. TPA did not inhibit glucagon-stimulated adenylate cyclase activity in a broken plasma membrane preparation unless Ca²⁺, phosphatidylserine and ATP were also present. It is suggested that TPA exerts its inhibitory effect on adenylate cyclase through the action of protein kinase C. This action is presumed to be exerted at the point of regulation of adenylate cyclase by guanine nucleotides.

【 授权许可】

Unknown