CATECHOLAMINE/OPIOID CONTROL OF VISCERAL REFLEXES IN NTS

儿茶酚胺/阿片类药物对 NTS 内脏反射的控制

基本信息

批准号：
6462986
负责人：
VIRGINIA M PICKEL
金额：
$ 11.7万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-07-01 至 2003-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6462986
关键词：
NMDA receptors adrenergic receptor baroreceptors baroreflex dopamine receptor electron microscopy glutamate receptor glutamates immunocytochemistry laboratory rat neurochemistry neurogenic hypertension neuroregulation neurotransmitter receptor neurotransmitter transport opioid receptor solitary tract nucleus substance P

项目摘要

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.

儿茶酚胺和阿片类药物可有效调节气压和 L-谷氨酸释放引起的化学感应反射和/或来自内脏传入的 P 物质，主要终止于孤束的内侧核 (m) 和连合核 (com) （NTS）。调节的导演取决于受体亚型、位置以及与 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，这些功能位点将在三项相互关联的研究中进行检查使用电子显微镜 (EM) 免疫细胞化学针对儿茶酚胺、阿片类药物、以及大鼠大脑 mNTS 和 comNTS 中的谷氨酸受体。研究我将测试以下假设：在这些区域中，α2A - 肾上腺素能受体 (alphs2A -AR) 和 D2 -多巴胺能受体 (D-R) 定位于 (I) 涉及存储或释放的站点他们各自的儿茶酚胺，与参与一致自动调节，或（ii）压力或化学感应传入或其目标，表明最有可能直接调制的位点心肺反射。研究二将检验以下假设： mu-阿片受体 (MOR) 和/或 sigma-阿片受体 (DOR) NTS 中的 (I) 神经元突触前或突触后位点含有内源性阿片肽、儿茶酚胺和/或 alpha2A -AR，表明阿片类药物自动调节和与儿茶酚胺的功能相互作用，(ii) 压力或化学感应传入，或含有 P 物质的末端，提示参与突触前兴奋性释放神经递质，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 的假设受体彼此之间分布有差异，以及表达 alpha2A -AR 或 MOR 的神经元，表明儿茶酚胺和/或阿片类药物调节可能至少部分地取决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是否或 NMDA 受体存在于 (I) 压力或化学感应传入，提示谷氨酸释放自动调节的位点，或（ii）二级感觉神经元，表明参与谷氨酸能兴奋。综合起来，结果将直接与理解病理生理学和设计的相关性治疗高血压、躯体交感神经痛和与大脑反射变化相关的缺血性脑损伤血流（量。