Abstract
Tumor-promoting phorbol esters may alter α1-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 3×10-7 M prazosin. PDBu also enhanced PE-induced slow responses 2- to 3-fold. These results suggest that PDBu enhances α1-adrenoceptor mediated PIE by potentiating slow Ca2+ channels, presumably through the activation of protein kinase C.
