REGULATION OF PERIPHERAL AUTONOMIC FUNCTION AND NEUROENDOCRINE RESPONSES

末梢自主功能和神经内分泌反应的调节

• 批准号: 6163075
• 负责人: I J KOPIN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6163075
• 关键词: 6 hydroxydopamine; autonomic nervous system; baroreceptors; baroreflex; dopamine; hypothalamus; isotope dilution method; laboratory rabbit; laboratory rat; microdialysis; neuroendocrine system; neuroregulation; neurotransmitter metabolism; neurotransmitter transport; norepinephrine; peripheral nervous system; phenylephrine; pituitary adrenal axis; solitary tract nucleus; yohimbine

The main objectives of this project are to determine the roles of catecholamines and their receptors in brain functions that regulate motor activity, neuroendocrine secretion, and autonomic function. Levels of monoamines and their metabolites in extracellular fluid in specific brain regions are monitored using in vivo microdialysis. Microdialysis probes with an attached infusion microcannulae provides a means for introducing drugs or isotopically-labeled compounds in the region of the microdialysis probe. The magnitude of release of NE and its metabolites in different nuclei within the hypothalamus is related to the degree of responses of the peripheral sympatho-adrenal medullary system and pituitary adrenocortical axis. In the hypothalamus, immobilization-induced increments in local release of norepinephrine are increased by systemic administration of yohimbine, an alpha2-adrenergic receptor blocking agent. In the striatum, we estimate the rate of dopamine release, reuptake and metabolism by combining microdialysis and tracer kinetics of[3H]-DA and using isotope dilution techniques similar to those being used in the plasma. In rats treated intracerebroventricularly with 6-hydroxydopamine the specific activity of recovered [3H]-DA is similar to that in the perfusate, whereas intact animals that had a specific activity was reduced about 100-fold. Simultaneously obtained values for the specific activities of [3H]dihydroxyphenylacetic acid ([3H]-DOPAC) and [3H]-homovanillic acid were about one-tenth of DA indicating that DA is largely deaminated within the neurons prior to release. The nucleus of the solitary tract (NTS), in the mediodorsal medulla of the brainstem, constitutes the main site of termination of afferents from arterial baroreceptors. In a study of single unit firing of NTS neurons in anesthetized rabbits, we found that most NTS neurons increase their firing rate after i.v. injection of phenylephrine, which increases blood pressure acutely by stimulating alpha1-adrenoceptors on vascular smooth muscle cells. In contrast, electrical stimulation of the PVN usually decreased NTS firing and attenuated or prevented phenylephrine-induced increases in NTS firing. The results support a model for acute resetting of the baroreflex during emotional distress.

该项目的主要目标是确定以下方面的作用： 调节运动神经元的脑功能中的儿茶酚胺及其受体 活动、神经内分泌和自主功能。水平 特定脑细胞外液中单胺类物质及其代谢产物 使用体内微透析监测区域。微透析探针 带有连接的输注微插管提供了一种用于引入 药物或同位素标记的化合物 探针NE及其代谢产物在不同组织中的释放量 下丘脑内的核团与 外周交感-肾上腺髓质系统和垂体 肾上腺皮质轴在下丘脑，固定诱导的 局部释放去甲肾上腺素的增量增加， 施用育亨宾，一种α 2-肾上腺素能受体阻断剂。 在纹状体，我们估计多巴胺的释放率，再摄取率和 代谢相结合的微透析和示踪动力学的[3 H]-DA和 使用类似于那些正在使用的同位素稀释技术 等离子体侧脑室注射6-羟基多巴胺 回收的[~ 3 H]-DA的比活性与 灌注液，而具有特定活性的完整动物减少 大约100倍。同时获得特定活动的值 [3 H]-二羟基苯乙酸（[3 H]-DOPAC）和[3 H]-高香草酸 大约是DA的十分之一，表明DA在很大程度上是脱氨基的， 神经元在释放之前。 孤束核（NTS）位于延髓背内侧， 脑干，构成终止传入的主要网站， 动脉压力感受器在对孤束核神经元单个单位放电的研究中， 麻醉家兔，我们发现大多数NTS神经元的放电增加， 静脉注射苯肾上腺素后的心率，苯肾上腺素可升高血压 通过刺激血管平滑肌上的α 1-肾上腺素能受体 细胞相反，PVN的电刺激通常减少， NTS放电和减弱或阻止苯肾上腺素诱导的增加， NTS发射。结果支持急性重置的模型， 压力感受器反射