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 microM) in Ca(2+)-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 Ca(2+)-containing solution. CPA inhibited oxytocin-induced Ca2+ release and contraction, the half and full inhibitory concentrations of CPA being 0.3 and 10 microM, respectively. In contrast, addition of CPA after Ca2+ loading exerted no significant inhibitory effects. 3. Oxytocin (10 nM) applied in Ca(2+)-containing solution induced rhythmic increases in both force and [Ca2+]i. CPA (10 microM) had no effect on oxytocin-induced rhythmic contractions. 4. At a high concentration (300 microM), 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 microM) 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.
Department of Pharmacology, Faculty of Medicine, University of Tokyo, Japan.
Y
Y
Kasai
M
M
Iino
O
O
Tsutsumi
Y
Y
Taketani
M
M
Endo
D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D005260:Female; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014590:Uterine Contraction / Q000187:drug effects*
D007211:Indoles; D013729:Terpenes; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D011188:Potassium; D002118:Calcium; C000543:cyclopiazonic acid