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°C. 2 Oxytocin (1 μm) 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 μm, 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 μm) had no effect on oxytocin‐induced rhythmic contractions. 4 At a high concentration (300 μm), CPA inhibited the rhythmic contractions induced by 10 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 μm) 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.