EFFECTS OF CYCLOPIAZONIC ACID ON RHYTHMIC CONTRACTIONS IN UTERINE SMOOTH-MUSCLE BUNDLES OF THE RAT

1 We studied the effects of cyclopiazonic acid (CPA) on rhythmic contractions and on Ca2+ uptake by the intracellular stores in longitudinal muscle strips of the rat uterus at 30 degrees C. 2 Oxytocin (1 mu M) in Ca2+-free solution induced a transient rise in the intracellular Ca2+ concentration ([Ca2+](i)) and contraction after Ca2+ loading of the stores in high-K+- and Ca2+-containing solution. CPA inhibited oxytocin-induced Ca2+ release and contraction, the half and full inhibitory concentrations of CPA being 0.3 and 10 mu M, respectively. In contrast, addition of CPA after Ca2+ loading exerted no significant inhibitory effects. 3 Oxytocin (10 nM) applied in Ca2+-containing solution induced rhythmic increases in both force and [Ca2+](i). CPA (10 mu M) had no effect on oxytocin-induced rhythmic contractions. 4 At a high concentration (300 mu M), CPA inhibited the rhythmic contractions induced by 1O nM oxytocin; the frequency and the peak height were decreased, and in many bundles contractions were completely abolished. These inhibitory effects were reversed after CPA washout. 5 CPA (300 mu M) inhibited the rate of rise of [Ca2+](i) due to depolarization induced by high-K+-containing solution. 6 These results suggest that low concentrations of CPA inhibit the loading of Ca2+ into intracellular stores in intact tissue strips, and that the Ca2+ stores are not directly involved in the uterine rhythmic contractions. It is also suggested that a high concentration of CPA inhibits the mechanism that is responsible for the generation of rhythmic contractions as well as voltage-dependent Ca2+ channels.