NEUROACTIVE AGENTS AND HYPOXIC EXCITATION OF BREATHING

一些神经活性物质被认为与 对呼吸的调节。两类推定 神经递质、速激肽(特别是P物质和 神经激动素A)和儿茶酚胺(尤其是多巴胺)似乎 严重参与神经轴的几个层面(颈动脉 躯体、岩神经节和髓质)在调节 低氧反应。例如，在颈动脉小体，P物质 (SP)和神经激肽A(NKA)具有兴奋作用； 多巴胺(DA)通常具有抑制作用。尽管有一种类似的 调控可能发生在其他站点，精确的相互作用 取决于直接的生化环境(包括 存在其他传输器)和局部解剖连接。 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。 这项拟议的研究使用跨学科的方法来 明确速激肽和多巴胺如何参与塑造 缺氧引起的呼吸增加。这项研究的目的是 目标： (A)确定速激肽和多巴胺能之间的相互作用 颈动脉小体中参与调节传入活动的元素 以及引起速激肽的释放和 多巴胺。猫的体内和体外制剂都会 被利用。 (B)界定多肽能和 化学感受器传入的多巴胺能表型特征 神经元。联合逆行追踪和免疫化学将 用来精确描述速激肽的定位和 颈动脉小体传入内肽的研究 在体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 一种模型系统来解释细胞的调节和可塑性 大鼠颈动脉小体传入的肽能和多巴胺能特征 体外培养。 (C)研究猫的速激肽和多巴胺在 纤维束核化学感受器信号的处理 孤立核和巨细胞旁核的解剖学和免疫组织化学研究 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 这项拟议的研究可能会揭示出基本的 生化组织原理，适用于神经症患者 系统作为一个整体。

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.