CATECHOLAMINE/OPIOID CONTROL OF VISCERAL REFLEXES IN NTS

儿茶酚胺和阿片类药物有效地调节压力和 归因于L-谷氨酸释放的化学感觉反射 和/或来自内脏传入的P物质，其主要终止于 孤束内侧核和连合核 （NTS）。 调节的方向依赖于受体 亚型、位置和与N-甲基-d-天冬氨酸的关联 （NMDA）和非NMDA型谷氨酸受体。 在这个项目中， 这些功能性地点将在三个相互关联的研究中进行审查 使用电子显微镜（EM）免疫细胞化学， 抗儿茶酚胺，阿片样物质， 和谷氨酸受体在大鼠脑的mNTS和comNTS。 研究一将测试假设，在这些地区，α 2A- 肾上腺素能受体（β 2A-AR）和D2 -多巴胺能受体 (D-R)（一）涉及储存或释放的场所 他们各自的儿茶酚胺，符合参与 自动调节，或（ii）压力或化学感觉传入或其 目标，表明最有可能直接调制的地点， 心肺反射 第二项研究将检验以下假设： μ-阿片受体（莫尔）和/或σ-阿片受体（DOR） 在NTS中定位于（I）神经元上的突触前或突触后位点 含有内源性阿片肽、儿茶酚胺和/或 α 2A-AR，提示阿片样物质自动调节和 与儿茶酚胺的功能性相互作用，（ii）气压或 化学感觉传入，或含有P物质的末梢， 暗示了突触前兴奋性神经递质的释放 神经递质，或（iii）二级感觉神经元，表明 参与对外周兴奋的突触后反应。 研究III将检验红藻氨酸受体和NMDA 受体相对于彼此差异地分布， 和表达α 2A-AR或莫尔的神经元，这表明 儿茶酚胺和/或阿片样物质调节可至少部分地 依赖于特定兴奋性氨基酸受体的存在。 本研究的其他具体目的是确定红藻氨酸盐是否 或NMDA受体存在于（I）压力或化学感受器上 传入神经，提示谷氨酸释放的自动调节位点， 或（ii）二级感觉神经元，表明参与 脑电兴奋。总之，结果将直接 与理解疾病的病理生理学和设计 新的治疗方法，高血压，躯体交感神经痛， 缺血性脑损伤与脑反射改变 血流

Catecholamines and opiates potently modulate baro- and chemosensory reflexes attributed to the release of L-glutamate and/or substance P from visceral afferents that terminate mainly in the medial (m) and commissural (com) nuclei of the solitary tract (NTS). The director of the modulation is dependent on the receptor subtype, location, and association with N-methyl-d-aspartate (NMDA) and non-NMDA type glutamate receptors. In this project, these functional sites will be examined in three interrelated studies using electron microscopic (EM) immunocytochemistry for the localization of antipeptide antisera against catecholamine, opioid, and glutamate receptors in the mNTS and comNTS of the rat brain. Study I will test the hypotheses that in these regions, alpha2A - adrenergic receptors (alphs2A -AR) and D2 -dopaminergic receptors (D-R) are localized to (I) sites involved in storage or release of their respective catecholamines, consistent with involvement in autoregulation, or (ii) baro- or chemosensory afferents or their targets, indicating the most probable sites for direct modulation of cardiorespiratory reflexes. Study II will test the hypotheses that mu-opioid receptors (MOR) and/or sigma-opioid receptors (DOR) in the NTS are localized to (I) pre- or postsynaptic sites on neurons containing endogenous opioid peptides, catecholamines, and/or alpha2A -AR, suggesting sites for opioid autoregulation and for functional interactions with catecholamines, (ii) baro- or chemosensory afferents, or substance P containing terminals, suggesting involvement in the presynaptic release of excitatory neurotransmitters, or (iii) second order sensory neurons, suggesting involvement in postsynaptic responses to peripheral excitation. Study III will test the hypothesis that kainate receptors and NMDA receptors are differentially distributed with respect to each other, and to neurons expressing alpha2A -AR or MOR, suggesting that catecholamine and/or opioid modulation may at least partially depend on the presence of a specific excitatory amino acid receptor. Other specific aims of this study are to determine whether kainate or NMDA receptors are present on (I) baro- or chemosensory afferents, suggesting sites for autoregulation of glutamate release, or (ii) second-order sensory neurons, suggesting involvement in glutamatergic excitation. Together, the results will have direct relevance to understanding the pathophysiology of, and devising new treatments for, hypertension, somato-sympathetic pain, and ischemic brain damage associated with reflex changes in cerebral blood flow.