Modulatory effect of protein kinase C activator on contractility of rat vas deferens.

ABSTRACT

The modulatory effect of the protein kinase C activator was examined on contraction of rat isolated vas deferens induced by constrictive agonists, noradrenaline (NA), ATP, BaCl2 and high K+. Phorbol 12,13-diacetate (PDA, 1 micromol/l) induced a transient extracellular Ca(2+)-dependent contraction while the inactive analogue, 4alpha-phorbol (1 micromol/l) had no effect. PDA significantly enhanced the peak amplitude of the contractile response to NA (0.1-10 micromol/l), ATP (100 micromol/l), Ba2+ (3 mmol/l) or high K+ (30 mmol/l). Staurosporine at 30 nmol/l reduced the enhancing effect of PDA on the agonist-induced contraction. NA (10 micromol/l) produced a phasic contraction followed by a sustained contraction, while ATP induced monophasic contraction. Pretreatment with nifedipine (10 nmol/l) had no effect on the phasic contraction induced by NA, but it significantly reduced ATP- or high K(+)-induced contraction. Staurosporine (30 nmol/l) alone attenuated the peak contractile response induced by NA or ATP but not by Ba2+. NA produced a transient contraction in Ca(2+)-free Krebs solution, and PDA (1 micromol/l) markedly enhanced this effect. These novel data indicate that activation of a protein kinase C-dependent mechanism not only affects contraction mediated by Ca2+ influx through voltage-sensitive Ca2+ channels, but also promotes intracellular Ca2+ release or intracellular Ca(2+)-mediated contractile mechanism in rat vas deferens.