SYMPATHOADRENAL AND CATECHOLAMINERGIC FUNCTION IN HEALTH AND DISEASE

健康和疾病中的交感肾上腺和儿茶酚胺能功能

• 批准号: 3846315
• 负责人: D S GOLDSTEIN
• 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/3846315
• 关键词: MAO inhibitors; adrenal medulla; alpha adrenergic receptor; catecholamines; dihydroxyphenylalanine; dopamine; heart innervation; homeostasis; human subject; hypertension; laboratory rat; microdialysis; neurochemistry; neuroendocrine system; neurotransmitter biosynthesis; norepinephrine; pheochromocytoma; physiologic stressor; positron emission tomography; radiotracer; saluresis; stress; sympathetic nervous system

Our research has focused on developing and applying methods for assessing the function of central and peripheral catecholaminergic systems and the coordination of these systems with other homeostatic systems in health, stress, and disease. Findings this year include: (1) Positron-emission tomographic (PET) scanning after systemic administration of 6-[18F]fluorodopamine ([18F]-6F-DA) provided a noninvasive, in vivo means to examine cardiac sympathetic innervation and function in humans. This approach can be used to identify clinical disorders of cardiac sympathetic regulation. (2) Clinical microneurographic and allied methods were established to measure skeletal sympathoneural activity directly to diagnose and monitor effects of treatments in a variety of neurocardiologic disorders. (3) An assay method for plasma levels of metanephrines was developed and validated. High normetanephrine levels were noted in all pheochromocytoma patients tested. (4) In healthy humans, dopamine (DA) in urine was found to be derived mainly from renal uptake of plasma DOPA, and low-dose DOPA infusion evoked a marked natriuresis and diuresis. The role of the DOPA-DA system and therapeutic effects of DOPA are being explored in sodium-retaining disorders. (5) Plasma levels of DOPA and dihydroxyphenylacetic acid (DOPAC) reflect in vivo tyrosine hydroxylation, a key aspect of catecholaminergic function. (6) In vivo microdialysis assessments of changes in extracellular fluid concentrations of catecholamines and their metabolites in brain showed: (a) glucocorticoids inhibited the function of alpha2-adrenoceptors on noradrenergic terminals in the paraventricular nucleus; (b) immobilization stress augmented norepinephrine (NE) release in the paraventricular nucleus of the hypothalamus and the central nucleus of the amygdala; (c) juvenile spontaneously hypertensive rats had increased alpha2-adrenoceptor-mediated restraint of catecholamine biosynthesis and NE release in the posterolateral hypothalamus and in the periphery, suggesting a basis for behavioral hyper-activity and hypertension in this rat strain; (d) locally administered glycine produced a net stimulatory effect on striatal DA release; and (e) chronic inhibition of monoamine oxidase A increased exocytotic cerebrocortical NE release. (7) Patterning of neuroendocrine stress responses during acute glucopenia in rats and humans refuted Selye's stress theory.

我们的研究重点是开发和应用评估方法， 中枢和外周儿茶酚胺能系统的功能， 这些系统与健康中的其他稳态系统的协调， 压力和疾病。 本年度的发现包括：（1）正电子发射 全身给药后的断层扫描（PET） 6-[18 F]氟多巴（[18 F]-6 F-DA）提供了一种非侵入性的体内方法， 研究人类心脏交感神经支配和功能。 这 方法可用于识别心脏的临床疾病 交感神经调节(2)临床显微神经摄影及相关方法 用于直接测量骨骼交感神经活动， 诊断和监测各种治疗的效果 神经心脏病(3)一种测定血浆中 开发并验证了肾上腺素。 偏高的normetanetamine水平 在所有检测的嗜铬细胞瘤患者中均观察到。(4)健康 人尿中的多巴胺（DA）主要来源于肾脏， 血浆多巴的摄取，低剂量多巴输液引起了显着的 尿钠排泄和利尿。 DOPA-DA系统的作用和治疗 多巴在钠潴留性疾病中的作用正在研究中。（五） 多巴和二羟苯乙酸（DOPAC）的血浆水平反映了 体内酪氨酸羟基化，这是儿茶酚胺能功能的关键方面。 (6)细胞外液变化的体内微透析评估 脑中儿茶酚胺及其代谢物的浓度显示： (a)糖皮质激素抑制α 2-肾上腺素受体的功能， 室旁核中的去甲肾上腺素能末梢;（B） 制动应激增加去甲肾上腺素（NE）的释放， 下丘脑室旁核和中央核 杏仁核;（c）幼年自发性高血压大鼠增加 α 2-肾上腺素受体介导的儿茶酚胺生物合成的抑制， 下丘脑后外侧和外周NE释放， 这表明了行为过度活跃和高血压的基础， 大鼠品系;（d）局部给予甘氨酸产生净刺激性 对纹状体DA释放的影响;和（e）单胺的慢性抑制 氧化酶A增加胞吐性肾上腺皮质NE释放。(7)图案化 大鼠急性血糖减少期间神经内分泌应激反应的研究， 人类反驳了塞利的压力理论