NONCLASSICAL TRANSMITTERS AND CARDIAC GANGLIA

非经典递质和心脏神经节

• 批准号: 2735264
• 负责人: DONALD B HOOVER
• 金额: $ 14.73万
• 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 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2735264
• 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 与心律不齐的产生有关，也有 触发冠状动脉血管痉挛的潜力。 心脏包含一个 详细的神经网络，包括交感神经，内在心脏 神经节和感官神经。 该提案基于最近的发现 感官神经元可以具有速素介导的传出功能 （TKS）和降钙素基因相关肽（CGRP）释放 他们的外围过程。 PI将评估TKS的假设 对冠状动脉流有直接影响并影响心脏的功能 神经节通过刺激胆碱能神经元上的术后TK受体。 该问题将在细胞，孤立的器官和整个动物上解决 使用豚鼠的水平。 PI还将检验以下假设 TK和/或CGRP的局部影响有助于心脏和冠状动脉 缺血和再灌注引起的反应。 六个具体目标是 定义以解决这些假设。 目标1。用孤立的心识别 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 SP和NKA在孤立的SP和NKA引起的反应的非胆碱能机制 心。 目标3。确定并表征对内源性TK的响应 孤立的心脏模型。 目标4。确定外源和 内源性TK在心脏内神经元和临时传播上的内源性TK 使用微电极记录技术的体外。 目标5。确定效果 心脏神经节中胆碱能神经元上的外源和内源性TK 体内。 目标6。使用选择性TK和CGRP拮抗剂来识别心脏和心脏 内源性感觉神经肽在孤立心脏和 缺血和再灌注期间麻醉豚鼠。 这条线 研究最终可以建立感觉神经元肽受体作为 特定心律不齐和冠状动脉血管痉挛治疗的靶标。