EFFECTS OF PHORBOL ESTERS ON CONTRACTION AND PROTEIN-KINASE-C ACTIVATION IN RABBIT AORTA

This study investigates the relationship between the contractile effic acy of phorbol esters and their ability to activate protein kinase C i n intact rabbit aorta. Phorbol dibutyrate (PDB) induced a maximal cont raction approximately 3.5-fold greater than that to phorbol myristate acetate (PMA). The magnitude of maximal PDB- and PMA-induced contracti on correlated with the magnitude of protein kinase C activation, as as sessed by the decrease in cytosolic protein kinase C activity. KCl (60 mM) did not potentiate the PMA-induced decrease in cytosolic protein kinase C activity. These results suggest that the lack of efficacy of PMA is due to its inability to activate protein kinase C in the intact rabbit aorta. It is speculated that the different contractile efficac ies of phorbol esters result from selective activation of protein kina se C isoforms, and that the amounts of these isoforms varies amongst v ascular tissues.