MODULATION OF CHEMICAL TRANSMISSION IN SENSORY RECEPTORS

感觉受体中化学传递的调节

• 批准号: 2262459
• 负责人: SALVATORE J FIDONE
• 金额: $ 25.14万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-07-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2262459
• 关键词: MODULATION; CHEMICAL; TRANSMISSION; SENSORY; RECEPTORS

The carotid body, an arterial chemoreceptor organ sensitive to O2 and CO2, possesses specialized pre-neural type I cells which contain an array of neurotransmitter agents. Current views hold that exposure to chemoreceptor stimuli initiates a complex cascade of transductive events in these cells, culminating in the release of excitatory transmitter agent(s) which activate closely apposed sensory fibers of the carotid sinus nerve (CSN). Numerous biophysical and neurochemical investigations have partially elucidated the mechanisms underlying chemotransduction and chemotransmission in this organ. However, it has become increasingly apparent that the chemosensitivity of the type I cell/sensory nerve ending complex is modulated by powerful extrinsic mechanisms involving direct neural innervation of this receptor complex, and by important intrinsic cellular mechanisms which are triggered by chemostimulation of the organ. Direct neural control consists of 1), an unidentified neural inhibitory component traveling in the CSN, and 2), sympathetic fibers in the gangliomerular nerve (GGN) which contact type I cells but whose function is likewise uncharacterized. Equally ill-defined are the intrinsic cellular mechanisms by which chemostimulation can invoke dramatic changes in the receptor complex, including type I cell hypertrophy, hyperplasia, and altered neurotransmitter levels and chemoreceptor thresholds. The experiments formulated here will use a multidisciplinary approach to investigate these neural and cellular mechanisms of chemoreceptor modulation. Our research plan consists of three specific aims: 1) we will identify the neurons and the neurotransmitter mechanisms involved in chemoreceptor inhibition via the CSN. These experiments utilize immunocytochemical, neurochemical and electrophysiological techniques to elucidate the roles of two putative inhibitory agents, nitric oxide and atrial natriuretic peptide, in modulation of chemoreceptor activity. 2) Studies of chemoreceptor modulation by the sympathetic innervation will use a unique in vitro superfusion chamber to assess direct preganglionic vs. postganglionic effects on type I cells and CSN activity. 3) Finally, the effects of chemostimulation and chronic denervation on cellular/molecular processes in type I cells will be evaluated in experiments designed to study the role of gene expression in regulation of the chemoresponse. These experiments involve the use of modern gene amplification and hybridization techniques. The ultimate aim of these studies is to clarify the synaptic and cellular processes which are key to chemoreceptor adaptations associated with natural stimulation.

颈动脉体，一种对O2敏感的动脉化学感受器器官 二氧化碳，具有包含阵列的专门的神经前I型细胞 神经递质剂。 当前的观点使这种暴露 化学感受器刺激引发了复杂的转导事件的复杂级联 在这些细胞中，最终在兴奋性发射机的释放中达到顶峰 激活颈动脉紧密含有的感觉纤维的代理 窦神经（CSN）。 大量生物物理和神经化学研究 已经部分阐明了趋化转导的机制和 该器官中的趋化递送。 但是，它变得越来越 显然，I型细胞/感觉神经的化学敏度 结束复合体受到涉及强大的外部机制的调节 该受体复合物的直接神经神经支配以及重要 固有的细胞机制是通过化学刺激触发的 器官。 直接神经控制包括1），一个身份不明的神经 抑制性成分在CSN中旅行，2）在2）中，同情纤维 神经节神经（GGN）接触I型细胞但其 功能同样没有特征。 同样明确的是 化学刺激可以调用的固有细胞机制 受体复合物的急剧变化，包括I型细胞 肥大，增生和神经递质水平改变， 化学感受器阈值。 这里制定的实验将使用 多学科研究这些神经和细胞的方法 化学感受器调制的机制。 我们的研究计划包括 三个具体目标：1）我们将确定神经元和 通过化学感受器抑制的神经递质机制通过 CSN。 这些实验利用免疫细胞化学，神经化学和 电生理技术阐明了两个推定的作用 抑制剂，一氧化氮和心房亚钠肽，中 化学感受器活性的调节。 2）化学感受器的研究 通过交感神经支配调节将使用独特的体外 超级灌注室评估直接的前牙齿前与gangionic 对I型细胞和CSN活性的影响。 3）最后， 在细胞/分子过程上的化学刺激和慢性神经支配 在I型细胞中，将在旨在研究的实验中评估 基因表达在化学响应调节中的作用。 这些 实验涉及现代基因扩增和 杂交技术。 这些研究的最终目的是 澄清突触和蜂窝过程，这是 与自然刺激相关的化学感受器适应。