BIOCHEMICAL EVALUATION OF ADRENERGIC FUNCTION

肾上腺素能功能的生化评价

• 批准号: 3945312
• 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/3945312
• 关键词: atrial natriuretic peptide; autonomic disorder; catecholamines; cocaine; desipramine; dihydroxyphenylalanine; homovanillate; hormone regulation /control mechanism; neuropharmacology; neurotransmitter metabolism; norepinephrine; plasma; sympathetic nervous system; synapses; vasoactive intestinal peptide

Measurement of levels of norepinephrine (NE), its metabolites, and precursors in plasma, urine, and cerebrospinal fluid have been developed and are being applied to studies of changes of these compounds in patients with various disorders of the autonomic nervous system and in rats after administration of drugs which alter synthesis, storage, release metabolism, or uptake of NE in sympathetic nerves. Drugs such as desipramine (or cocaine) which block uptake, enhance apparent release of norepinephrine into the circulation and diminish formation of its deaminated metabolites, DHPG and MHPG. L-DOPA is formed in the sympathetic neurones and overflows into the blood. It may be an important source of extraneuronal dopamine and act as a neurohumoral agent. Patients with orthostatic hypotension have parallel decreases in excretion of homovanillic acid (HVA), the major metabolite of dopamine, and norepinephrine metabolites (MHPG and VMA). A similar relationship holds in animals and humans treated with debrisoquin to inhibit peripheral catecholamine metabolism. Using monkeys treated with MPTP to destroy central dopaminergic neurones, we have established the validity of extrapolating the regression line relating HVA to MHPG to measure the brain HVA production. This has been done in both urine and plasma of monkeys. A means of rapid enzymatic conversion of 18F-dopa to 18F-dopamine has been developed. The 18F-dopamine is to be administered as a precursor of endogenous 18F-norepinephrine to study by PET scanning the peripheral sympathetic neurones in various disease states.

去甲肾上腺素（NE）及其代谢物水平的测量， 血浆、尿液和脑脊液中的前体物质已被 开发并应用于这些变化的研究 患有各种自主神经疾病的患者的化合物 神经系统和大鼠服用药物后 改变 NE 的合成、储存、释放代谢或摄取 交感神经。 地昔帕明（或可卡因）等药物 阻断摄取，增强去甲肾上腺素的表观释放 循环并减少其脱氨基代谢物的形成， DHPG 和 MHPG。 L-DOPA在交感神经中形成 神经元并溢出到血液中。 这可能是一个重要的 神经元外多巴胺的来源并充当神经体液 代理人。 直立性低血压患者有类似的症状 高香草酸（HVA）的排泄减少，这是主要的 多巴胺代谢物和去甲肾上腺素代谢物（MHPG 和VMA）。 动物和人类之间也存在类似的关系 用异喹啉治疗以抑制外周儿茶酚胺 代谢。 使用经过 MPTP 处理的猴子进行破坏 中枢多巴胺能神经元，我们已经确定了有效性 将 HVA 与 MHPG 相关的回归线外推至 测量大脑 HVA 的产生。 这已在两个中完成 猴子的尿液和血浆。 一种快速酶解的方法 已开发出 18F-多巴至 18F-多巴胺的转化。 这 18F-多巴胺作为内源性多巴胺的前体施用 通过 PET 扫描外周血来研究 18F-去甲肾上腺素 各种疾病状态下的交感神经元。