EFFECTS OF PHORBOL 12,13-DIBUTYRATE AND H-7 IN EXTRAVASCULAR SMOOTH-MUSCLE CONTRACTION

The effect of the activator, phorbol 12,13-dibutyrate (PDB), and the i nhibitor, H-7, of protein kinase C (PKC) has been assayed in rat uteru s. PDB increases the amplitude of spontaneous contractions of rat uter us and this effect does not occur in the presence of H-7 or nifedipine . PDB did not modify the KCl-induced tonic contraction but H-7 relaxed it, in a concentration-dependent way. PDB inhibited the contraction i nduced by oxytocin in rat uterus incubated in Ca-free solution and rel axed the tonic contraction induced by oxytocin in this medium. The rel axing effect of PDB on oxytocin-induced contraction was not modified b y H-7. Thus H-7 relaxed, in a concentration-dependent way, the tonic c ontractions induced by oxytocin and vanadate in the rat uterus incubat ed in Ca-free medium. Our results suggest a dual effect of PDB related to calcium, and a direct and PKC-independent inhibitory effect of H-7 .