Irvine, F and Pyne, N J and Houslay, M D (1986) The phorbol ester TPA inhibits cyclic AMP phosphodiesterase activity in intact hepatocytes. FEBS Letters, 208 (2). pp. 455-459. ISSN 0014-5793Full text not available in this repository. (Request a copy from the Strathclyde author)
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 EC50 of 0.39 ng/ml and 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.
|Keywords:||1-methyl-3-isobutylxanthine, 3',5'-cyclic-AMP phosphodiesterases, animals, cyclic AMP, drug synergism, glucagon, liver, male, rats, tetradecanoylphorbol acetate, Pharmacy and materia medica, Biochemistry, Structural Biology, Cell Biology, Genetics, Molecular Biology, Biophysics|
|Subjects:||Medicine > Pharmacy and materia medica|
|Department:||Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences|
|Depositing user:||Pure Administrator|
|Date Deposited:||14 Nov 2011 14:19|
|Last modified:||23 Sep 2016 02:31|