REGULATION OF VAGAL SUBSTANCE P SYNTHESIS IN VITRO

P物质是一种广泛分布的神经肽，已在 迷走神经感觉神经节的胞体和纤维 从他们身上双向散发出来。在迷走神经感觉刺激下， P物质不仅可以在体内的中央终端释放 延髓也在周围神经末梢，在那里可能 对心血管、呼吸系统和胃肠有重要影响 功能。 这个项目将研究一些基本未知的因素，这些因素调节着 P物质在感觉迷走神经中的合成和运输。 利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物质是可行的 超过24小时，这些研究将检验P物质 合成通过以下三种方式之一进行调节：1)由激素或 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)改变 双极传入(中枢)投射的神经传递 感觉纤维。P物质和从头物质的合成和转运 合成的放射性标记物质P将在添加过程中进行测量 激素或选定的神经递质的外植体培养基或 电刺激外植体周围和中心 投射。合成/运输的变化将与 两个主要的细胞内第二信使系统环磷酸腺苷的变化 和多磷肌醇代谢。体内研究也将是 以确定是否改变了P物质的合成和运输 与其基础和刺激释放的类似变化相结合 中枢脑干和外周迷走神经感觉终末。 迷走神经在心血管疾病中具有重要功能，如 心律失常和高血压，肺的支气管痉挛障碍和 各种胃肠道疾病。含有感觉性迷走神经的P物质 可能在这些情况下起着重要的传入和传出作用。 了解其合成和运输的调节将提供一种 为认识和更有选择性的治疗奠定基础 对这些疾病的迷走神经部分进行干预。这些研究还包括 将增进对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.