BRAIN AMINES--REGULATION AND FUNCTION

脑胺——调节和功能

• 批准号: 3782454
• 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/3782454
• 关键词: acetylcholine; animal tissue; basal ganglia; brain; dopamine; epinephrine; histamine; hypothalamus; innervation; microdialysis; neuropharmacology; neurophysiology; neurotransmitter biosynthesis; neurotransmitter metabolism; neurotransmitter transport; nicotinic receptors; norepinephrine; nuclear magnetic resonance spectroscopy; physiologic stressor; secretion; serotonin; stress; tissue /cell culture

The main objectives of this project are to: (1) examine formation, release, metabolism and disposition of brain biogenic amines and their alterations after administration of drugs or toxin~induced models of human disease; (2) determine the physiologic role of biogenic amines in mediating responses to stress; and (3) develop methods that can be adapted to study of brain biogenic amine metabolism in humans. In vivo microdialysis has been used to monitor levels of monoamines and their metabolites in extracellular fluid in various regions of the hypothalamus and in the basal ganglia. Receptors and trans~porters have been examined in vitro using cells from different regions of brain: in cell lines cultured from the hypothalamus. Results of studies using microdialysis have shown that norepinephrine (NE) release in the paraventricular nucleus (PVN) varies with the stressor, being greatest with immobilization and least with hypoglycemia. Furthermore, by unilateral interruption of ascending noradrenergic pathways in the brain stem, the degree of innervation of the hypothalamic nuclei can be assessed. Locally administered glycine, intro~duced into the regions of the tip of a microdialysis probe, elicits dose~dependent, strychnine~sensitive dopamine release. The interaction of glycine with nicotinic acetylcholine receptors in bovine adrenal medullary membranes (demonstrated in vitro by NMR) suggests that the amino acid modulates this receptor at one of two sites whichare strychnine sensitive. Endogenous serotonin also appears to influence pamine release from the striatum.

本项目的主要目标是：（1）检查形成， 脑内生物胺的释放、代谢和处置 给药后的变化或毒素诱导的模型 人类疾病;（2）确定生物胺的生理作用， 调解对压力的反应;（3）开发可以 适用于人脑生物胺代谢的研究。 体内微透析已被用于监测单胺的水平， 它们的代谢物在细胞外液中的不同区域的 下丘脑和基底神经节。 受体和转运体有 在体外使用来自大脑不同区域的细胞进行了检查： 从下丘脑培养的细胞系。 使用微透析的研究结果表明，去甲肾上腺素 (NE)室旁核（PVN）中的释放随 应激源，制动时最大，低血糖时最小。 此外，通过单侧阻断去甲肾上腺素能神经元的上行通路， 脑干中的神经通路，下丘脑的神经支配程度 核可以被评估。局部给予甘氨酸，引入 微透析探针的尖端区域，具有剂量依赖性， 士的宁~敏感的多巴胺释放。甘氨酸与 牛肾上腺髓质膜的烟碱型乙酰胆碱受体 （通过NMR在体外证明）表明氨基酸调节 这个受体位于士的宁敏感的两个位点之一。 内源性5-羟色胺似乎也会影响多巴胺的释放， 纹状体