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.

颈动脉体是一种对 O2 和氧气敏感的动脉化学感受器器官 CO2，拥有专门的前神经 I 型细胞，其中包含阵列 神经递质剂。 目前的观点认为，暴露于 化学感受器刺激引发一系列复杂的转导事件 在这些细胞中，最终释放兴奋性递质 激活颈动脉紧密相连的感觉纤维的药剂 窦神经（CSN）。 大量的生物物理和神经化学研究 部分阐明了化学转导的机制 该器官中的化学传递。 然而，它已经变得越来越 显然，I 型细胞/感觉神经的化学敏感性 结束复合体受到强大的外在机制的调节，包括 该受体复合物的直接神经支配，并且通过重要 由化学刺激触发的内在细胞机制 器官。 直接神经控制包括 1)、一个未识别的神经 抑制成分在 CSN 中传播，2)、交感纤维 神经节小球神经 (GGN) 与 I 型细胞接触，但其 功能同样没有特征。 同样不明确的还有 化学刺激可以调用的内在细胞机制 受体复合物（包括 I 型细胞）发生巨大变化 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 多学科方法来研究这些神经和细胞 化学感受器调节机制。 我们的研究计划包括 三个具体目标：1）我们将识别神经元和 神经递质机制参与化学感受器抑制 南航。 这些实验利用免疫细胞化学、神经化学和 电生理学技术阐明两种假定的作用 抑制剂、一氧化氮和心钠素 化学感受器活性的调节。 2) 化学感受器的研究 通过交感神经支配的调节将使用独特的体外 灌注室评估直接节前与节后 对 I 型细胞和 CSN 活性的影响。 3）最后，效果 细胞/分子过程的化学刺激和慢性去神经支配 I 型细胞将在旨在研究的实验中进行评估 基因表达在化学反应调节中的作用。 这些 实验涉及使用现代基因扩增和 杂交技术。 这些研究的最终目的是 阐明关键的突触和细胞过程 与自然刺激相关的化学感受器适应。