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The phorbol ester, TPA inhibits glucagon‐stimulated adenylate cyclase activity
Author(s) -
Heyworth Clare M.,
Whetton Anthony D.,
Kinsella Anne R.,
Houslay Miles D.
Publication year - 1984
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(84)81364-2
Subject(s) - adenylate kinase , cyclase , glucagon , cholera toxin , phosphodiesterase , chemistry , medicine , protein kinase c , endocrinology , phorbol , protein kinase a , biochemistry , receptor , biology , signal transduction , enzyme , hormone
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 Ca 2+ , 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.