PURINOCEPTOR CONTROL OF SURFACTANT SECRETION

肺透明膜病是该病的主要致病因素。 与早产有关的死亡率。这种病现在是 被理解为与缺乏合成和分泌 肺泡II型细胞表面活性物质。建议的研究是 旨在测试表面活性物质从 肺上皮细胞由P2-嘌呤受体介导 激活，磷脂酰肌醇周转，钙动员， 蛋白激酶C的激活，以及随后的磷酸化 调节表面活性物质释放的特定细胞蛋白。 其次，提出了这一反应的成熟 系统，是新生儿适应能力所必需的 宫外生，发生在围产期。据预测， 这种反应系统的成熟是由荷尔蒙 并且存在着治疗的可能性 P2-嘌呤受体系统的调节。系统的研究将 用来展示P2-嘌呤受体， 磷脂酰肌醇多磷酸周转，钙 动员、前列腺素生产、蛋白激酶C 激活与蛋白激酶C依赖的磷酸化 反应以确定参与的可能的细胞机制 表面活性物质对P2-嘌呤受体激活的释放反应。 上述活动的确定和特征将是 在成年大鼠的II型细胞中进行，并与 表面活性物质的释放特征。在澄清了 以上是成体细胞中的调节事件，更难研究 这一系统的发育和成熟是由胎儿决定的 将进行肺部检查。这些后来的实验将利用 胎儿II型细胞无血清短期组织培养 确定可能的体液调节的媒介 P2-嘌呤受体各组分的成熟 响应系统。这项研究的总体目标是 确定可能涉及的细胞机制 表面活性物质释放的成熟可能在 肺透明膜病和其他呼吸道疾病的发病机制 早产婴儿和成人的问题。

Hyaline membrane disease is a major factor in the morbidity and mortality associated with premature birth. This disease is now understood to be related to lack of synthesis and secretion of surfactant from alveolar Type II cells. The proposed study is designed to test the hypothesis that surfactant release from pulmonary epithelial cells is mediated by P2-purinoceptor activation, phosphatidylinositol turnover, calcium mobilization, protein kinase C activation, and subsequent phosphorylation of specific cellular proteins regulating release of surfactant. Secondly, it is proposed that the maturation of this response system, required for the ability of the newborn to adapt to extrauterine life, occurs in the perinatal period. It is predicted that the maturation of this response system is hormonally mediated and that there exists the potential for therapeutic regulation of the P2-purinoceptor system. Systematic studies will be undertaken to demonstrate P2-purinoceptors, phosphatidylinositol polyphosphate turnover, calcium mobilization, prostaglandin production, protein kinase C activation, and protein kinase C dependent phosphorylation reactions to identify the possible cellular mechanisms involved in surfactant release responses to P2-purinoceptor activation. Identification and characterization of the above activities will be performed in adult rat Type II cells and correlated with the characteristics of surfactant release. After clarification of the above regulatory events in the adult cell, more difficult studies to determine the development and maturation of this system is fetal lung will be performed. These later experiments will utilize short-term tissue culture of fetal Type II cells in serum-free medium to determine possible humoral regulation of the maturation of the various components of the P2-purinoceptor response system. The overall objective of the study is to determine the possible cellular mechanisms involved in the maturation of sufactant release which may play a role in the pathogenesis of hyaline membrane disease and other respiratory problems of both the prematurely born infant and adults.