Zhang L, Pearce W J, Longo L D
Department of Pharmacology, Loma Linda University School of Medicine, CA 92350, USA.
Eur J Pharmacol. 1995 Apr 28;289(2):375-82. doi: 10.1016/0922-4106(95)90116-7.
To elucidate the role of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) as a second messenger through which noradrenaline regulates contractions of the uterine artery, we present here studies designed to characterize simultaneously the noradrenaline-mediated contractions and Ins(1,4,5)P3 formation in isolated uterine arteries from near-term pregnant sheep. Noradrenaline stimulated a rapid increase of Ins(1,4,5)P3 formation with the peak at 30 second. Simultaneous measurement of noradrenaline-induced contractile responses and Ins(1,4,5)P3 formation revealed a significant linear correlation between these two events. In accordance with the contractile results, the noradrenaline-mediated inositol phosphate accumulation was blocked by prazosin (0.1 microM), but not by yohimbine (0.1 microM). Pre-treatment of tissues with pertussis toxin (200 ng/ml, 3 h) failed to block noradrenaline-induced inositol phosphate accumulation. We conclude that, in the uterine artery of late pregnancy, the alpha 1-adrenoceptor-elicited contraction, at least the initial phasic component, is predominantly mediated by the formation of Ins(1,4,5)P3, leading to release of Ca2+ from intracellular stores.
为阐明肌醇1,4,5-三磷酸（Ins(1,4,5)P3）作为去甲肾上腺素调节子宫动脉收缩的第二信使的作用，我们在此展示了旨在同时表征来自近足月妊娠绵羊的离体子宫动脉中去甲肾上腺素介导的收缩和Ins(1,4,5)P3形成的研究。去甲肾上腺素刺激Ins(1,4,5)P3形成迅速增加，在30秒时达到峰值。同时测量去甲肾上腺素诱导的收缩反应和Ins(1,4,5)P3形成，发现这两个事件之间存在显著的线性相关性。与收缩结果一致，去甲肾上腺素介导的肌醇磷酸积累被哌唑嗪（0.1微摩尔）阻断，但未被育亨宾（0.1微摩尔）阻断。用百日咳毒素（200纳克/毫升，3小时）预处理组织未能阻断去甲肾上腺素诱导的肌醇磷酸积累。我们得出结论，在妊娠晚期的子宫动脉中，α1-肾上腺素能受体引发的收缩，至少是初始的相性成分，主要由Ins(1,4,5)P3的形成介导，导致Ca2+从细胞内储存释放。
