CONTROL OF MEMBRANE ACTIVITY BY NEUROTRANSMITTERS

在许多组织中，神经递质和激素占据受体 引发磷脂酰肌醇 4,5-二磷酸的水解 细胞质膜。 这似乎是一个信号传输 涉及产生两个假定的第二信使的系统 - 肌醇 1,4,5-三磷酸 (IP3) 和二酰甘油 (DG)。 这项研究 检查该系统的机制和功能的各个方面。 具体 目标包括研究： 1. 内质网膜中 IP3 的高亲和力结合位点。 2. 纯化磷脂酰肌醇合酶的特性及影响因素 调节其活动。 3. IP3 和/或 DG 在级联机制中可能发挥的作用 通过水解磷脂酰肌醇进一步生产 DG 内质网状膜。 4. IP3和DG作为触发的第二信使的作用 对乙酰胆碱的组织特异性、生物合成、适应性反应。 要检查的反应是输出蛋白（消化 酶）在胰腺腺泡细胞中，以及血浆的合成 禽类盐腺细胞中的膜酶 NaK-ATP 酶。 5. 体内锂盐治疗对机体的影响 小鼠大脑和胰腺中的磷酸肌醇信号传输系统， 以及对乙酰胆碱的最终反应（酶分泌和蛋白质 合成）在胰腺中。 该方法包括：放射光亲和化合物的合成； 酶的分离；亚细胞膜组分的孵育， 分散的细胞制剂和组织切片；准备和分析 色谱技术。 这些实验的结果将进一步加深对 磷酸肌醇信号传递系统，以及该系统的作用 在生物合成的诱导中，发生的适应性变化 对神经系统中的神经递质和激素的反应 其他地方。 它们还将有助于理解 锂盐。

In many tissues, receptor-occupancy by neurotransmitters and hormones triggers the hydrolysis of phosphatidylinositol 4,5-bisphosphate in the plasma membrane of the cell. This appears to be a signal transmission system which involves the generation of two putative second messengers - myo-inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DG). This study examines aspects of the mechanism and function of this system. Specific aims include studies of: 1. High-affinity binding sites for IP3 in endoplasmic reticular membranes. 2. The properties of purified phosphatidylinositol synthase, and factors which regulate its activity. 3. The possible role of IP3 and/or DG in a cascade mechanism for the further production of DG by hydrolysis of phosphatidylinositol in endoplasmic reticular membranes. 4. Roles of IP3 and DG as second messengers for the triggering of tissue-specific, biosynthetic, adaptive responses to acetylcholine. Responses to be examined are the synthesis of export protein (digestive enzymes) in the pancreas acinar cell, and the synthesis of the plasma membrane enzyme, NaK-ATPase, in the avian salt gland cell. 5. The effects of treatment with lithium salts in vivo on the phosphoinositide signal transmission system in mouse brain and pancreas, and on end responses to acetylcholine (enzyme secretion and protein synthesis) in the pancreas. The methodology includes: synthesis of radiophotoaffinity compounds; isolation of enzymes; incubation of subcellular membrane fractions, dispersed cell preparations, and tissue slices; preparative and analytical chromatographic techniques. The results from these experiments will further an understanding of the phosphoinositide signal transmission system, and of the role of this system in the induction of the biosynthetic, adaptive changes which occur in response to neurotransmitters and hormones in the nervous system and elsewhere. They will also contribute to an understanding of the actions of lithium salts.