REGULATION OF VAGAL SUBSTANCE P SYNTHESIS IN VITRO

P物质是一种广泛分布的神经肽， 迷走神经感觉神经节的细胞体和纤维 从他们身上发出双向辐射。 在迷走神经感觉刺激后， P物质不仅可以在中央终端释放， 延髓，但也在周围神经末梢， 对心血管、呼吸和胃肠道有重要影响 功能 这个项目将研究在很大程度上未知的因素， P物质在感觉迷走神经内的合成和运输。 使用结状神经节和迷走神经的外植体， 证明在体外合成和转运P物质 超过24小时，这些研究将检验P物质 合成以三种方式之一调节：1）通过激素或 直接作用于感觉细胞体的神经递质，2）通过 传入神经刺激的频率或强度或3）通过改变 在双极的传入（中枢）投射的神经传递中 感觉纤维 P物质的合成和转运以及从头合成 将在添加过程中测量合成的放射性标记物质P 激素或选定的神经递质的外植体培养基， 电刺激外植体外周和中枢后， 预测。 合成/转运的变化将与 两个主要的细胞内第二信使系统，环AMP 和多磷酸肌醇代谢。 还将进行体内研究。 以确定是否改变了P物质的合成和转运 与其基础和刺激释放的类似变化相关联， 中枢脑干和外周迷走神经感觉末梢。 迷走神经在心血管疾病中具有重要功能， 心律失常和高血压、肺的支气管痉挛性疾病和 各种胃肠道疾病。 含感觉迷走神经的P物质 可能在这些条件下发挥重要的传入和传出作用。 了解它的合成和运输的调节将提供一个 为识别和更有选择性的治疗奠定基础， 对这些疾病的迷走神经成分进行干预。 这些研究还 将增强对P物质和神经肽调节的理解， 神经系统的其他部分，包括大脑。

Substance P, a widely distributed neuropeptide, has been identified within cell bodies of the sensory ganglia of the vagus nerve and the fibers emanating bidirectionally from them. Upon vagal sensory stimulation, substance P may be released not only at central terminals within the medulla oblongata but also at peripheral nerve endings where it may importantly influence cardiovascular, respiratory and gastrointestinal function. This project will study the factors, largely unknown, regulating the synthesis and transport of substance P within the sensory vagus nerve. Using explants of nodose ganglion and vagus nerve that have been demonstrated to synthesize and transport substance P in vitro for periods exceeding 24 hours, these studies will test the hypothesis that substance P synthesis is regulated in one of three ways: 1) by hormones or neurotransmitters acting directly on sensory cell bodies, 2) by the frequency or intensity of afferent neural stimulation or 3) by alterations in neurotransmission of the afferent (central) projection of the bipolar sensory fibers. Synthesis and transport of substance P and of de novo synthesized radiolabeled substance P will be measured during the addition to the explant medium of hormones or selected neurotransmitters or following electrical stimulation of explant peripheral and central projections. Changes in synthesis/transport will be correlated with alterations in two major intracellular second messenger systems, cyclic AMP and polyphosphoinositide metabolism. In vivo studies will also be performed to determine whether altered substance P synthesis and transport is coupled to similar changes in its basal and stimulated release at central brainstem and peripheral vagal sensory terminals. The vagus nerve has important functions in cardiovascular diseases such as arrythmia and hypertension, bronchospastic disorders of the lung and a variety of gastrointestinal disorders. Sensory vagus-contained substance P may play important afferent and efferent roles in those conditions. Understanding the regulation of its synthesis and transport will provide a groundwork for the recognition of and more selective therapeutic intervention in the vagal component of those disorders. These studies also will enhance understanding of substance P and neuropeptide regulation in other parts of the nervous system, including the brain.