NEUROACTIVE AGENTS AND HYPOXIC EXCITATION OF BREATHING

神经活性剂和缺氧呼吸兴奋

• 批准号: 3356895
• 负责人: NEIL S CHERNIACK
• 金额: $ 15.6万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-30 至 1992-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3356895
• 关键词: action potentials; afferent nerve; carotid body; catecholamines; cats; chemoreceptors; dopamine; dopamine receptor; electrophysiology; ganglions; gene expression; high performance liquid chromatography; histochemistry /cytochemistry; hypercapnia; immunochemistry; laboratory rabbit; laboratory rat; neural transmission; neurons; neuropeptides; neurotransmitters; pulmonary respiration; radioimmunoassay; radiotracer; respiration regulatory center; respiratory hypoxia; solitary tract nucleus; substance P; tissue /cell culture; tyrosine 3 monooxygenase

A number of neuroactive substances have been implicated in the regulation of breathing. Two classes of putative neurotransmitters, the tachykinins (particularly substance P and neurokinin A) and catecholamines (especially dopamine) seem to be critically involved at several levels of the neuraxis (the carotid body, the petrosal ganglion, and the medulla) in mediating the hypoxic response. At the carotid body, for instance, substance P (SP) and neurokinin A (NKA) have excitatory effects while dopamine (DA) usually inhibits. Although a similar kind of regulation may occur at other sites, the precise interaction depends on the immediate biochemical environment (including the presence of other transmitters) and local anatomic connections. In addition, the interplay among SP, NKA and DA may vary as hypoxic stimulation is maintained. The proposed research uses cross-disciplinary approaches to define how tachykinins and dopamine participate in shaping the respiratory increase caused by hypoxia. This study has as its goals: (a) To determine the interplay of tachykinins and dopaminergic elements in the carotid body in modulating the afferent activity of single fibers and in causing the release of tachykinins and dopamine. Both in vivo and in vitro preparations of the cat will be used. (b) To define the expression and regulation of peptidergic and dopaminergic phenotypic traits in chemoreceptor afferent neurons. Combined retrograde tracing and immunochemistry will be used to delineate precisely the localization of tachykinins and peptides within carotid body afferents and to define the relationship of peptidergic and dopaminergic expression in vivo. In addition, cultured rat petrosal ganglion neurons will be used as a model system to elucidate the regulation and plasticity of peptidergic and dopaminergic traits of carotid body afferents in vitro. (c) To examine in cats the role of tachykinins and dopamine in the processing of chemoreceptor signals in the nucleus tractus solitarius and nucleus paragigantocellularis using anatomic and electrophysiologic techniques, as well as by measuring the release of tachykinins and dopamine. By defining transmitter interaction in these chemoreceptor pathways the proposed research may shed light on fundamental principles of biochemical organization, applicable to the nervous system as a whole.

许多神经活性物质与 呼吸的调节。 两类假定的 神经递质，速激肽（特别是P物质和 神经激肽A）和儿茶酚胺（尤其是多巴胺）似乎 严重累及神经轴（颈动脉）的几个水平 体、岩神经节和髓质）在介导 低氧反应 例如，在颈动脉体， (SP)和神经激肽A（NKA）具有兴奋作用， 多巴胺（DA）通常抑制。 虽然类似的 调节可能发生在其他位点，精确的相互作用 取决于直接的生物化学环境（包括 存在其它发射器）和局部解剖学连接。 此外，SP、NKA和DA之间的相互作用可能会有所不同， 维持低氧刺激。 拟议的研究使用跨学科的方法， 定义速激肽和多巴胺如何参与塑造 缺氧引起的呼吸增加。 这项研究作为其 目标： (a)为了确定速激肽和多巴胺能的相互作用， 颈动脉体中的成分在调节传入活动中的作用 单纤维和引起速激肽的释放， 多巴胺 猫的体内和体外制剂都将 被利用 (b)为了明确肽能和肽调节蛋白的表达和调节， 化学感受器传入的多巴胺能表型特征 神经元 结合逆行追踪和免疫化学将 可用于精确描绘速激肽的定位， 肽在颈动脉体传入，并确定 体内肽能和多巴胺能表达的关系。 此外，培养的大鼠岩神经节神经元将被用作 一个模型系统，以阐明调节和可塑性， 颈动脉体传入的肽能和多巴胺能特性 体外 (c)在猫中检查速激肽和多巴胺在 化学感受器信号在束核中的处理 孤束核和旁巨细胞核的解剖学和 电生理技术，以及通过测量释放 速激肽和多巴胺 通过定义这些化学感受器中的递质相互作用， 拟议的研究可能揭示的基本途径 生物化学组织的原则，适用于神经 整个系统。