Premium
The phorbol ester TPA inhibits cyclic AMP phosphodiesterase activity in intact hepatocytes
Author(s) -
Irvine Fiona,
Pyne Nigel J.,
Houslay Miles D.
Publication year - 1986
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(86)81068-7
Subject(s) - phosphodiesterase , glucagon , adenylate kinase , chemistry , cyclase , intracellular , phosphodiesterase inhibitor , protein kinase c , medicine , phorbol , tetradecanoylphorbol acetate , endocrinology , hepatocyte , cyclic nucleotide phosphodiesterase , protein kinase a , enzyme , phorbol ester , biochemistry , biology , in vitro , hormone
Treatment of intact hepatocytes with the phorbol ester 12‐ O ‐tetradecanoyl phorbol 13‐acetate (TPA) potentiated the ability of glucagon to increase intracellular cyclic AMP concentrations. This effect was dose‐dependent upon TPA, exhibiting an EC 50 of 0.39and such activation was observed at both saturating and sub‐saturating concentrations of glucagon. However, this stimulatory effect of TPA was completely abolished by the presence of the cyclic AMP phosphodiesterase inhibitor 1‐isobutyl‐3‐methylxanthine, when TPA now inhibited the glucagon‐stimulated increase in intracellular cyclic AMP concentrations. It is suggested that, as well as inhibiting glucagon‐stimulated adenylate cyclase activity, TPA also inhibits cyclic AMP phosphodiesterase activity in intact hepatocytes. Treatment of either hepatocyte homogenates or purified cyclic AMP phosphodiesterase with TPA failed to show any direct inhibitory effect of TPA on activity showing that TPA did not exert any direct inhibitory action on phosphodiesterase activity. However, homogenates made from hepatocytes that had been pre‐treated with TPA did show a reduced cyclic AMP phosphodiesterase activity. It is suggested that TPA might inhibit cyclic AMP phosphodiesterase activity through phosphorylation by C‐kinase.