Phorbol ester potentiates alpha 1-adrenoceptor-mediated positive inotropic effect in rat papillary muscle.
Tumor-promoting phorbol esters may alter alpha 1-adrenoceptor-mediated cardiac response by stimulating protein kinase C activity. We investigated the effect of phorbol-12,13-dibutyrate (PDBu) on the positive inotropic effect (PIE) in rat left ventricular papillary muscle. PDBu (1-100 nM) potentiated the phenylephrine (PE)-induced PIE in a dose- and time-dependent manner. The PIE induced by PE and PDBu was abolished by pretreatment with 3 x 10(-7) M prazosin. PDBu also enhanced PE-induced slow responses 2- to 3-fold. These results suggest that PDBu enhances alpha 1-adrenoceptor-mediated PIE by potentiating slow Ca2+ channels, presumably through the activation of protein kinase C.
D000818:Animals; D002316:Cardiotonic Agents; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*
D002316:Cardiotonic Agents; D007473:Ion Channels; D010703:Phorbol Esters; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D011224:Prazosin