PURINOCEPTOR CONTROL OF SURFACTANT SECRETION

肺透明膜病是发病的主要因素， 与早产有关的死亡率。 这种疾病现在 据了解，这与缺乏合成和分泌有关。 肺泡II型细胞的表面活性剂。 拟定研究 旨在检验表面活性剂从 P2-嘌呤受体介导的肺上皮细胞凋亡 活化，磷脂酰肌醇周转，钙动员， 蛋白激酶C激活，随后磷酸化 调节表面活性剂释放的特定细胞蛋白质。 第二，提出了这种反应的成熟 系统，新生儿适应能力所需的 宫外孕，发生在围产期。 据预测 这种反应系统的成熟 介导的，并存在治疗的潜力， P2-嘌呤受体系统的调节。 系统研究将 来证明P2-嘌呤受体， 磷脂酰肌醇多磷酸钙周转率 动员，前列腺素产生，蛋白激酶C 活化和蛋白激酶C依赖性磷酸化 反应，以确定可能的细胞机制参与 表面活性剂释放响应于P2-嘌呤受体活化。 上述活动的识别和特征将 在成年大鼠II型细胞中进行，并与 表面活性剂释放特性。 在澄清了 以上的调控事件在成人细胞，更困难的研究， 决定这一系统发育成熟的是胎儿 肺将被执行。 这些后期实验将利用 胎儿II型细胞无血清短期组织培养 介质，以确定可能的体液调节， P2-嘌呤受体各种成分的成熟 响应系统 研究的总体目标是 确定可能的细胞机制参与 表面活性剂释放的成熟可能在 肺透明膜病和其他呼吸道疾病的发病机制 早产儿和成年人的问题。

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.