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 inhibitor, H-7, of protein kinase C (PKC) has been assayed in rat uterus. PDB increases the amplitude of spontaneous contractions of rat uterus 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 induced by oxytocin in rat uterus incubated in Ca-free solution and relaxed the tonic contraction induced by oxytocin in this medium. The relaxing effect of PDB on oxytocin-induced contraction was not modified by H-7. Thus H-7 relaxed, in a concentration-dependent way, the tonic contractions induced by oxytocin and vanadate in the rat uterus incubated 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.