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.