ARACHIDONIC ACID METABOLITES AND UTERINE CONTRACTIONS

这个项目的广泛、长期的目标是阐明 分娩过程中子宫收缩的调控机制 并找到预防早产的新疗法，早产是一种主要的 我国围产期正常和发病率的原因。 催产素(OT)、催产素受体和子宫肌层的作用 将对分娩中的缝隙连接进行调查。 在目前的项目中，私家侦探发现抑制内源性PG 合成延缓了产妇子宫和子宫中OT受体的形成 怀孕时间过长。在这个相互竞争的续篇中，假设 催产素可能会自动刺激子宫肌层自身受体的形成 通过蜕膜检测OT受体的激活和PG的释放。加班 受体阻断将由特定的长效OT受体产生 孕鼠体内的拮抗剂(由P.I.和他的合作者开发) 从怀孕第19天开始。催产素受体失活的影响 子宫PG释放、蜕膜和肌层OT受体形成的研究 子宫肌层缝隙连接的发展将被确定。PGS将 通过特异性放射免疫测定(RIA)进行定量；OT受体 由放射性配基-受体结合分析和缝隙连接确定 电子显微镜。催产素拮抗剂作为产酸分解药的潜力 将研究早产的预防，并与萘普生进行比较。 钠，一种PG合成抑制剂，具有已知的酵解作用。效应 用催产素拮抗剂和萘普生钠治疗妊娠期， 将对分娩和妊娠结局进行研究。 PG对OT受体和缝隙连接形成的作用机制 将会被追查。体内和体外大鼠模型将被用来 确定PG是否直接或间接通过其 黄体溶解作用。

The broad, long-term objectives of this project are to elucidate the regulatory mechanisms controlling uterine contractions in parturition and to find new therapy for the prevention of premature birth, a major cause of perinatal normality and morbidity in this country. Specifically, the roles of oxytocin (OT), OT receptors and myometrial gap junctions in labor will be investigated. In the current project, the P.I. found that suppression of endogenous PG synthesis delayed OT receptor formations in the parturient uterus and prolonged gestation. In this competing continuation, the hypothesis that OT may auto-stimulate its own receptor formation in the myometrium via decidual OT receptor activation and PG release will be examined. OT receptor blockade will be produced by specific long-acting OT receptor antagonists (developed by P.I. and his collaborators) in pregnant rats beginning on day 19 of gestation. Effects of OT receptor inactivation on uterine PG release, decidual and myometrial OT receptor formations and myometrial gap junction developments will be determined. PGs will be quantified by specific radioimmunoassays (RIAs); OT receptors determined by radioligand-receptor binding assays and gap junctions by electron microscopy. The potential of OT antagonists as tocolytics for prevention of preterm labor will be studied and compared with naproxen sodium, a PG synthesis inhibitor with known tocolytic action. Effects of OT antagonist and naproxen sodium treatment on gestational period, parturition and outcome of pregnancy will be studied. The mechanism of action of PG on OT receptor and gap junction formations will be pursued. In vivo and in vitro rat models will be utilized to determine whether PG exerts its effects directly or indirectly via its luteolytic action.