NONCLASSICAL TRANSMITTERS AND CARDIAC GANGLIA

非经典递质和心脏神经节

• 批准号: 6030702
• 负责人: DONALD B HOOVER
• 金额: $ 14.95万
• 依托单位: EAST TENNESSEE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6030702
• 关键词: autoradiography; bradykinin; calcitonin gene related peptide; ganglion cell; guinea pigs; heart innervation; heart pharmacology; histochemistry /cytochemistry; ischemia; microelectrodes; neural transmission; neuropeptide receptor; nitric oxide; perfusion; reperfusion; sympathetic ganglion; tachykinin

DESCRIPTION (Adapted from Applicant's Abstract): Neural mechanisms have been implicated in the generation of cardiac arrhythmias and also have the potential for triggering coronary vasospasm. The heart contains an elaborate neural network that includes sympathetic nerves, intrinsic cardiac ganglia and sensory nerves. This proposal is based on the recent discovery that sensory neurons can have efferent functions mediated by tachykinins (TKs) and calcitonin gene-related peptide (CGRP) that are released from their peripheral processes. The PI will evaluate the hypothesis that TKs have direct effects on coronary flow and affect the function of cardiac ganglia by stimulating postjunctional TK receptors on cholinergic neurons. The problem will be addressed at cellular, isolated organ and whole animal levels using the guinea pig. The PI will also test the hypothesis that local effects of the TKs and/or CGRP contribute to cardiac and coronary responses evoked by ischemia and reperfusion. Six specific aims have been defined to address the hypotheses. Aim 1. Use isolated hearts to identify the responses mediated by specific types of TK receptor and autoradiographic methods to localize and quantify these receptors. Aim 2. Determine the importance of TK receptor types, nitric oxide, cholinergic neurons and noncholinergic mechanisms to responses evoked by SP and NKA in isolated hearts. Aim 3. Identify and characterize responses to endogenous TKs in the isolated heart model. Aim 4. Determine effects of exogenous and endogenous TKs on intracardiac neurons and intraganglionic transmission in vitro using microelectrode recording techniques. Aim 5. Determine effects of exogenous and endogenous TKs on cholinergic neurons in cardiac ganglia in vivo. Aim 6. Use selective TK and CGRP antagonists to identify cardiac and coronary effects of endogenous sensory neuropeptides in isolated hearts and anesthetized guinea pigs during ischemia and reperfusion. This line of investigation could ultimately establish sensory neuron peptide receptors as targets for therapy of specific cardiac arrhythmias and coronary vasospasm.

描述（改编自申请人的摘要）：神经机制已经 与心律失常的发生有关，并且还具有 触发冠状血管痉挛的可能性。 心脏含有一个 复杂的神经网络，包括交感神经、内在心脏神经 神经节和感觉神经。 该提案基于最近的发现 感觉神经元可以具有由速激肽介导的传出功能 (TK) 和降钙素基因相关肽 (CGRP) 他们的外围过程。 PI 将评估传统知识的假设 直接影响冠状动脉血流，影响心脏功能 通过刺激胆碱能神经元上的连接后 TK 受体来抑制神经节。 该问题将在细胞、分离器官和整个动物方面得到解决 使用豚鼠的水平。 PI 还将检验以下假设： TK 和/或 CGRP 的局部效应有助于心脏和冠状动脉 缺血和再灌注引起的反应。 制定了六项具体目标 定义来解决假设。 目标 1. 使用离体心脏来识别 由特定类型的 TK 受体和放射自显影介导的反应 定位和量化这些受体的方法。 目标 2. 确定 TK 受体类型、一氧化氮、胆碱能神经元和 孤立的 SP 和 NKA 引起反应的非胆碱能机制 心。 目标 3. 识别并描述对内源传统知识的反应 离体心脏模型。 目标 4. 确定外源性和 内源性TKs对心内神经元和神经节内传递的影响 体外使用微电极记录技术。 目标 5. 确定效果 外源性和内源性 TK 对心神经节胆碱能神经元的影响 体内。 目标 6. 使用选择性 TK 和 CGRP 拮抗剂来识别心脏和 离体心脏内源性感觉神经肽的冠状动脉效应 缺血和再灌注期间麻醉的豚鼠。 这条线的 研究最终可能确定感觉神经元肽受体为 治疗特定心律失常和冠状血管痉挛的目标。