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

• 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
• 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

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有效地调节Baro-和 L-谷氨酸释放引起的化学感觉反射 和/或P物质来自内脏传入，主要终止于 孤束核的内侧核(M)和连合核(Com) (新界别)。调制的导向器取决于受体 亚型、位置及其与N-甲基-d-天冬氨酸的关系 (NMDA)和非NMDA型谷氨酸受体。在这个项目中， 这些功能部位将在三个相互关联的研究中进行研究 使用电子显微镜(EM)免疫细胞化学技术 抗儿茶酚胺、阿片类、 和谷氨酸受体在大鼠脑内的mNTS和comNTs。 研究I将检验假设，在这些区域，α2a- 肾上腺素能受体(α-AR)和D2-多巴胺能受体 (D-R)定位于(I)涉及储存或释放的地点 它们各自的儿茶酚胺，与参与 自动调节，或(Ii)气压或化学感觉传入或其 目标，指示最有可能直接调制的位置 心肺反射。第二项研究将检验以下假设 Mu阿片受体(MOR)和/或Sigma阿片受体(DOR) 在NTS中定位于(1)神经元上的突触前或突触后 含有内源性阿片肽、儿茶酚胺和/或 Alpha2a-AR，建议阿片类药物自动调节和 与儿茶酚胺的功能相互作用，(Ii)巴-或 化学感觉传入或含有P物质的终末， 提示参与了突触前兴奋性神经元的释放 神经递质，或(Iii)二级感觉神经元，表明 参与突触后对外周兴奋的反应。 研究III将检验红藻氨酸受体和NMDA的假说 受体相对于彼此是不同的分布， 以及表达α2a-AR或MOR的神经元，这表明 儿茶酚胺和/或阿片类药物调节至少部分 取决于特定兴奋性氨基酸受体的存在。 这项研究的其他具体目的是确定凯恩特 或NMDA受体存在于(I)压力或化学感觉上 传入，提示谷氨酸释放的自动调节部位， 或(Ii)二级感觉神经元，表明参与了 谷氨酸能兴奋。总而言之，结果将直接 与理解和设计的病理生理学有关 治疗高血压、躯体交感疼痛和 与脑反射改变相关的缺血性脑损伤 血液流动。