TROPHISM AND TRANSMITTER RELEASE IN SYMPATHETIC NEURONS

交感神经元的营养和递质释放

基本信息

批准号：
2215152
负责人：
ARUN R. WAKADE
金额：
$ 18.09万
依托单位：
WAYNE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-09-01 至 1995-06-30
项目状态：
已结题

项目摘要

Since 1967, my research goal is focused on the issue of mechanism of transmitter released from sympathetic neuroeffector organs. In 1980, tissue culture technique was adopted with a hope that a pure population of sympathetic neurons (SN) would be available to study the molecular mechanism of transmitter release by determining the role of calcium ions (Ca) and other second messengers. Toward such a goal, several noradrenergic properties of cultured SN were established over the past 11 funding years. During the next support period we intend to probe further into the mechanism of release of norepinephrine (NE) by applying techniques not available in the past. Four major aspects of neurosecretion will be covered in the proposed research plan. 1. Physiological and pharmacological characteristics of 3H-NE release from two specialized regions of SN (I.E. cell body and nerve terminal or growth cone) will be evaluated. 2. Movements of Ca will be monitored in the cell body and the growth cones to know how these regions handle Ca and respond to agents that modulate 3H-NE release by affecting Ca. 3. Involvement of second messengers will be investigated on 3H-NE release and Ca movements to know how protein kinase C, inositol 1,4,5-triphosphate and cAMP cross-communicate to modulate release and neuronal Ca. 4. Trophic influence of heart cells on 3H_NE release and Ga-movements will be determined to know if heart cells modulate the release by affecting Ga movements in SN. Since the current proposal includes methods that are capable of giving more direct information, it is anticipated that upon completion of the present study a comprehensive picture will emerge concerning the role of Ca and other second messengers in the transmitter release process. Most important, these studies will provide new insights regarding the trophic influence of heart cells on their fields of innervation during growth and development. A number of preliminary results support the feasibility of the proposed research plan.

自1967年以来，我的研究目标集中在机制问题上。交感神经效应器官释放的递质。 1980年，纸巾采用养殖技术的目的是希望能够培养出纯种的种群交感神经元（SN）将可用于研究分子通过确定钙离子的作用来确定递质释放的机制 (Ca) 和其他第二信使。为了实现这一目标，一些去甲肾上腺素能药物培养 SN 的特性是在过去 11 年的资助中建立的。在下一个支持期间，我们打算进一步探讨通过应用技术释放去甲肾上腺素（NE）的机制过去可用。将涵盖神经分泌的四个主要方面在拟议的研究计划中。 1.生理和药理 SN 的两个专门区域（即 3H-NE）释放的特征细胞体和神经末梢或生长锥）将被评估。 2. 将在细胞体和生长锥中监测 Ca 的移动，以了解这些区域如何处理 Ca 并对调节 3H-NE 的药物做出反应通过影响 Ca 来释放。 3. 第二信使的参与研究 3H-NE 释放和 Ca 移动，了解蛋白激酶如何发挥作用 C、肌醇1,4,5-三磷酸和cAMP交叉通讯进行调节释放和神经元 Ca。 4. 心脏细胞对 3H_NE 的营养影响将确定释放和 Ga 运动以了解心脏细胞是否调节通过影响SN中的Ga运动来释放。由于当前的提案包括能够提供更多信息的方法直接信息，预计在完成目前的研究将得出关于 Ca 和的作用的全面图景发射机释放过程中的其他第二信使。最重要的是，这些研究将为营养影响提供新的见解心脏细胞在生长和发育过程中的神经支配区域。一个大量初步结果支持拟议方案的可行性研究计划。