Phorbolester inhibits alpha 1-adrenoceptor mediated phosphoinositide breakdown in cardiomyocytes.
The regulation of and the intracellular events following alpha 1-adrenergic receptor stimulation of myocardium are not completely understood. The alpha 1-adrenergic stimulation of phosphoinositide breakdown was examined in a culture of neonatal rat ventricular myocytes and the influence of a protein kinase C activator, phorbol 12-myristate 13-acetate, on this process was studied. Inositolphosphate accumulation was stimulated by phenylephrine (EC50 5 microM) in the presence of 10 mM LiCl. The increase was antagonized by prazosin (10(-6) M) but not by propranolol (10(-6) M). The rate of inositolphosphate accumulation after prolonged alpha 1-adrenoceptor stimulation decreased without clear evidence of depletion of the membrane phosphatidylinositolbisphosphate pool. Phorbol ester treatment (IC50 10(-8) M) led to a dose-dependent inactivation of alpha 1-adrenoceptor stimulated phosphoinositide breakdown. These findings provide evidence that protein kinase C plays a role in the regulation of alpha 1-adrenoceptor sensitivity.
Meij
J T
JT
Department of Biochemistry I, Medical Faculty, Erasmus University Rotterdam, The Netherlands.
Lamers
J M
JM
D000818:Animals; D002478:Cells, Cultured; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*
D010703:Phorbol Esters; D010716:Phosphatidylinositols; D011942:Receptors, Adrenergic, alpha