STRUCTURAL AND FUNCTIONAL STUDIES--UTERINE SMOOTH MUSCLE

以下建议概述了我们对细胞间 在控制哺乳动物的生殖功能中起重要作用。 为卵巢和子宫细胞的调节提供了证据 称为间隙连接的表面结构， 各种小的调节和信息分子的交换 细胞之间的接触。建立的解剖学基础 分娩过程中子宫平滑肌的协调活动是由于 子宫肌层细胞间隙连接的出现， 偶联，从而在分娩期间形成单个电合胞体。 本提案中概述的研究旨在提供一个独特的 调节机制分析的实验方法 哺乳动物子宫中的细胞间通讯。的目的 研究内容包括：（a）研究雌激素和孕激素对 子宫肌层间隙连接的形成，并比较 子宫肌层间隙连接的通透性特性与 血管平滑肌细胞：（B）检验以下假设： 子宫肌层中缝隙连接的通透性可由cAMP调节， 肌醇磷脂信号转导途径;（c）开发 子宫肌层细胞-颗粒层共培养系统，以分析 影响缝隙连接通道的调节机制的差异 渗透性：（d）测试电子致密沉积物的假设 与受体介导的缝隙连接膜相关 cAMP途径的激活代表腺苷酰捕获的Ca++ 环化酶衍生的焦磷酸阴离子。由于早产与 超过60%的婴儿死亡，减少这种危险需要研究 维持怀孕和开始分娩的因素。的结果 这些研究将有助于更好地了解子宫肌层 分娩时的收缩力，并希望， 有效的宫缩抑制剂。

The following proposal outlines our interest in the role of intercellular communication in the control of reproductive function in mammals. Evidence is provide for the regulation of ovarian and uterine cell surface structures termed gap junctions which are involved in the direct exchange of a variety of small regulatory and informational molecules between cells in contact. The anatomical basis for the establishment of coordinated uterine smooth muscle activity during labor is due to the appearance of myometrial cell gap junctions which facilitates electrical coupling and thereby a single electrical syncytium during parturition. The studies outlined in this proposal are designed to provide a unique experimental approach to the analysis of the mechanisms regulating intercellular communication in the mammalian uterus. The objective of the research are: (a) To study the action of estrogen and progesterone on the formation of myometrial gap junctions in vitro and compare the permeability properties of myometrial gap junctions with those of vascular smooth muscle cells: (b) to test the hypothesis that the permeability of gap junctions in myometrium can be modulated by cAMP and the inositol phospholipid signal transduction pathways; (c) to develop myometrial cell-granulosa co-culture systems in order to analyze differences in the regulatory mechanisms affecting gap junction channel permeability: (d) to test the hypothesis that electron dense deposits associated with gap junction membrane following receptor mediated activation off the cAMP pathway represents Ca++ trapped by adenylyl cyclase derived pyrophosphate anions. As prematurity is associated with over 60% of all infant deaths, reduction of this hazard requires research on the factors that maintain pregnancy and initiate labor. The results of these studies will lead to a better understanding of uterine myometrial contractility during parturition and hopefully, to the development of effective tocolytic agents.