Molecular mechanisms regulating the effects of oxytocin on myometrial intracellular calcium.
Molecular mechanisms regulating the effects of oxytocin on myometrial intracellular calcium.
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DOI：
10.1007/978-1-4615-4871-3_35
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发表时间：
1998
影响因子：
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通讯作者：
Barbara M. Sanborn;K. Dodge;Monju Monga;Ansha Qian;Wei Wang;C. Yue
中科院分区：
文献类型：
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作者：
Barbara M. Sanborn;K. Dodge;Monju Monga;Ansha Qian;Wei Wang;C. Yue
催产素通过几种机制刺激子宫肌层细胞内钙的增加。几条证据表明催产素受体在功能上与刺激磷脂酶C活性的Gαq/11类GTP结合蛋白偶联。磷脂酶C激活后产生的IP 3可触发细胞内钙库的钙释放。发现催产素刺激的子宫肌层细胞内钙的增加在细胞外钙的存在下比在其不存在下更大，表明催产素也对钙内流有影响。抗G αq/11抗体可抑制催产素刺激的子宫肌层膜GT3活性和磷脂酶C活性。Gαq共转染增强了催产素对转染催产素受体质粒的COS细胞中磷酸肌醇转换的刺激作用。催产素受体的细胞内结构域的共转染导致不同程度的干扰催产素刺激的磷酸肌醇营业额。这些数据表明，不止一个胞内结构域参与催产素受体/G蛋白偶联。这发生在子宫肌层细胞和用表达受体的质粒转染的COS细胞中。其抑制机制涉及蛋白激酶A的作用，可能间接靶向Gαq/11/磷脂酶C偶联步骤。
Oxytocin stimulates an increase in intracellular calcium in uterine myometrium by several mechanisms. Several lines of evidence indicate that the oxytocin receptor is functionally coupled to GTP-binding proteins of the Gαq/11class which stimulate phospholipase C activity. The IP3generated as a result of phospholipase C activation can trigger release of calcium from intracellular stores. The finding that the oxytocin-stimulated increase in intracellular calcium in myometrial cells is greater in the presence of extracellular calcium than that in its absence indicates that oxytocin also has effects on calcium entry. This action is nifedipine-insensitive but may involve indirect stimulation of calcium entry through release-operated channels.An anti-Gαq/11antibody inhibits both oxytocin-stimulated GTPase activity and phospholipase C activity in myometrial membranes. The stimulation by oxytocin of phosphoinositide turnover in COS cells transfected with a plasmid expressing the oxytocin receptor is enhanced by cotransfection of Gαq. Co-transfection of intracellular domains of the oxytocin receptor causes varying degrees of interference with oxytocin-stimulated phosphoinositide turnover. The data suggest that more than one intracellular domain is involved in oxytocin receptor/G-protein coupling.Oxytocin receptor stimulation of phospholipase C is inhibited by cAMP. This occurs in myometrial cells and in COS cells transfected with a plasmid expressing the receptor. The inhibitory mechanism involves the action of protein kinase A and is probably targeted indirectly at the Gαq/11/phospholipase C coupling step.