ARACHIDONIC ACID METABOLITES AND UTERINE CONTRACTIONS

该项目的广泛的长期目标是阐明 分娩时控制子宫收缩的调节机制 并找到新的治疗方法来预防早产，这是一个主要的 导致围产期正常和发病率在这个国家。 具体来说，催产素（OT），OT受体和子宫肌层的作用， 将研究分娩中的缝隙连接。 在目前的项目中，P.I.发现内源性PG的抑制 催产素合成延迟了分娩子宫中催产素受体的形成， 妊娠期延长 在这个竞争的延续中，假设 OT可以自动刺激子宫肌层中自身受体的形成， 通过蜕膜OT受体激活和PG释放的作用。 OT 受体阻滞剂将由特异性长效OT受体产生 拮抗剂（由P.I.和他的合作者）在怀孕的大鼠中 从妊娠第19天开始。 OT受体失活的影响 对子宫PG释放、蜕膜和子宫肌层OT受体形成的影响 并测定子宫肌层间隙连接的发育。 PG将 通过特异性放射免疫测定（RIA）定量; OT受体 通过放射性配体-受体结合测定和间隙连接测定， 电镜 OT拮抗剂作为宫缩抑制剂的潜力 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，具有已知的安胎作用。 影响 催产素拮抗剂和那普利钠治疗的妊娠期， 将研究分娩和妊娠结局。 PG对OT受体和缝隙连接形成的作用机制 将被追捕。 体内和体外大鼠模型将用于 确定PG是否直接或间接通过其 溶黄体作用。

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.