López Bernal A, Rivera J, Europe-Finner G N, Phaneuf S, Asbóth G
University of Oxford, Nuffield Department of Obstetrics and Gynaecology, Headington, UK.
Adv Exp Med Biol. 1995;395:435-51.
Parturition results from the establishment of phasic regular uterine contractions. Contractility in myometrial smooth muscle is stimulated by an increase in intracellular calcium ([Ca2+i]) which activates myosin light chain phosphorylation leading to increased myosin ATPase activity and enhanced rate of acto-myosin cross bridge formation. G proteins play a pivotal role in smooth muscle activation and relaxation by coupling cell membrane receptors to effector enzymes and ion channels. G alpha(s) and G alpha(i) stimulate and inhibit adenylyl cyclase, respectively and control cAMP formation. G alpha(q) stimulates phospholipase C resulting in the formation of two second messengers: inositol 1,4,5-trisphosphate (InsP3) which releases Ca2+ from the sarcoplasmic reticulum, and 1,2-diacylglycerol which activates protein kinase C. The oxytocin receptor stimulates myometrial contractility by increasing [Ca2+i] through both pertussis toxin resistant (G alpha(q)) and pertussis toxin sensitive (?G alpha (i)) pathways. beta-Adrenoceptors and prostaglandin EP2 receptors promote relaxation via G alpha(s)-adenylyl cyclase. The concentration of myometrial oxytocin receptors is five-times higher in pregnant compared to non-pregnant myometrium but decreases in samples obtained during labour. When myometrial slices are challenged with oxytocin there is a rapid increase in InsP3 levels with a time course which is similar to the rise in [Ca2+i] provoked by oxytocin in cultured myometrial cells. The formation of InsP3 in response to oxytocin in myometrial tissue at term is similar in samples obtained before and after the onset of labour. G alpha(q) and G alpha(i) are expressed at similar levels in non-pregnant and in pregnant myometrium obtained before or during labour. By contract, G alpha(s) levels are higher in pregnant compared to non-pregnant myometrium and decrease in samples obtained during labor. These changes in G alpha(s) are paralleled by prostaglandin E2-induced adenylyl cyclase activity in the same tissues. Parturition may be the consequence of downregulation of pathways that favour uterine quiescence by increasing cAMP formation, resulting in a relative dominance of stimulatory receptors that increase InsP3/Ca2+ availability.
分娩源于阶段性规律子宫收缩的建立。子宫肌层平滑肌的收缩性受细胞内钙（[Ca2+]i）增加的刺激，这会激活肌球蛋白轻链磷酸化，导致肌球蛋白ATP酶活性增加以及肌动球蛋白横桥形成速率加快。G蛋白通过将细胞膜受体与效应酶和离子通道偶联，在平滑肌的激活和舒张中起关键作用。Gα(s)和Gα(i)分别刺激和抑制腺苷酸环化酶，并控制cAMP的形成。Gα(q)刺激磷脂酶C，导致形成两种第二信使：肌醇1,4,5 - 三磷酸（InsP3），它从肌浆网释放Ca2+；以及1,2 - 二酰基甘油，它激活蛋白激酶C。催产素受体通过百日咳毒素抗性（Gα(q)）和百日咳毒素敏感性（?Gα(i)）途径增加[Ca2+]i，从而刺激子宫肌层收缩。β - 肾上腺素能受体和前列腺素EP2受体通过Gα(s) - 腺苷酸环化酶促进舒张。与未孕子宫肌层相比，孕子宫肌层中催产素受体的浓度高五倍，但在分娩期间获取的样本中会降低。当用催产素刺激子宫肌层切片时，InsP3水平会迅速升高，其时间进程与培养的子宫肌层细胞中催产素引起的[Ca2+]i升高相似。足月时，子宫肌层组织中对催产素反应的InsP3形成在分娩开始前后获取的样本中相似。Gα(q)和Gα(i)在未孕和分娩前或分娩期间获取的孕子宫肌层中表达水平相似。相比之下，与未孕子宫肌层相比，孕子宫肌层中Gα(s)水平更高，而在分娩期间获取的样本中会降低。这些Gα(s)的变化与同一组织中前列腺素E2诱导的腺苷酸环化酶活性平行。分娩可能是通过增加cAMP形成来促进子宫静止的途径下调的结果，导致增加InsP3/Ca2+可用性的刺激性受体相对占优势。
