SYMPATHOADRENAL AND CATECHOLAMINERGIC FUNCTION IN HEALTH AND DISEASE

与特定异常相关的独特神经化学模式 在儿茶酚胺的生物合成、储存、释放、处置和 代谢在几种遗传性或获得性疾病中都有描述。 患有门克斯病(一种铜代谢紊乱)的儿童 多巴胺-β-羟化酶(DBH)活性降低的证据， 多巴：二羟基苯甘醇(DHPG)的比例总是增加，使 宫内诊断和早期治疗。二氢蝶呤还原酶(DHPR) 缺乏会导致一种非典型的苯丙酮尿症。我们的发现是 低水平但可检测到的多巴酚类和其他儿茶酚类物质 没有DHPR意味着在人类中，DHPR并不是绝对需要的 儿茶酚胺合成。家族性自主神经障碍(FD)患者有 特征，明显的神经化学表型，具有较高的 血浆DOPA：DHPG和正常血浆NE、DA和二羟基苯乙酸 (DOPAC)水平。这种表型预示着一种突变会导致停滞 外周儿茶酚胺能系统的分化。患有疾病的患者 遗传性MAO-A缺陷症的DHPG水平很低，而 MAO-B缺乏的患者没有，提供了一种手段 区分这两种亚型的神经化学缺陷 酵素。诊断的血浆游离(非结合)后肾上腺素水平 嗜铬细胞瘤比任何其他神经化学测试都要好。几个 研究评估了儿茶酚胺能神经化学与 生理和病理生理状态或药物治疗。一项研究 交感神经直接记录与神经化学方法相结合 为糖皮质激素诱导的交感神经抑制提供了第一个证据 在人类中，表明两个人之间潜在的重要相互作用 身体的主要应力效应系统。长时间低头卧床是 用作太空飞行期间长期暴露在零重力环境中的模型。 神经化学结果表明，慢性交感神经抑制 伴随着立位耐受性，这种耐受性总是发生在 暴露在地球引力之下。一种特有的神经循环 模式被发现先于神经性心源性晕厥，伴有钝性 非低血压下体负压时前臂去甲肾上腺素溢出增加 增强的血浆肾上腺素(EPI)反应。在一个有害羞的病人身上- Drager综合征和多发性骨髓瘤，体外测试支持 自身免疫性疾病的致病机制。协作的结果 对氯氮平的研究表明，这种新型抗神经药作用于几个 外周去甲肾上腺素能功能的一些方面。我们获得了证据证明 交感神经末梢上的功能性刺激性β-肾上腺素受体 人的前臂，没有发现功能性刺激受体的证据 血管紧张素II。在人类中，已发现的主要递质调节剂 交感神经的释放似乎是抑制的，由 α2-肾上腺素能受体。

Distinctive neurochemical patterns associated with specific abnormalities in catecholamine biosynthesis, storage, release, disposition, and metabolism were described in several genetic or acquired diseases. Children with Menkes' disease, a disorder of copper metabolism, had evidence for decreased activity of dopamine-beta-hydroxylase (DBH), with DOPA:dihydroxyphenylglycol (DHPG) ratios invariably increased, enabling in utero diagnosis and early treatment. Dihydropteridine reductase (DHPR) deficiency causes an atypical form of phenylketonuria. Our finding of low but detectable levels of DOPA and other catechols in a patient with absent DHPR implies that in humans, DHPR is not absolutely required for catecholamine synthesis. Patients with familial dysautonomia (FD) had a characteristic, distinct neurochemical pheno-type, with high ratios of plasma DOPA:DHPG and normal plasma NE, DA, and dihydroxyphenylacetic acid (DOPAC) levels. The phenotype predicts a mutation that produces arrested differentiation of peripheral catecholaminergic systems. Patients with inherited deficiency of MAO-A had very low levels of DHPG, whereas patients with deficiency of MAO-B did not, providing a means to distinguish neurochemically deficiencies of the two isoforms of the enzyme. Plasma levels of free (unconjugated) metanephrines diagnosed pheochromocytoma better than did any other neurochemical test. Several studies assessed catecholaminergic neurochemical correlates of physiological and pathophysiologic states or drug treatments. A study combining direct sympathetic nerve recording with neurochemical methods provided the first evidence for glucocorticoid-induced sympathoinhibition in humans, indicating a potentially important interaction between two of the body's main stress effector systems. Prolonged head-down bed rest was used as a model of chronic exposure to zero-gravity during space flight. Neurochemical findings indicated that chronic sympathoinhibition accompanies the orthostatic intolerance that always occurs during re- exposure to the earth's gravity. A characteristic neurocirculatory pattern was found to precede neurocardiogenic syncope, with blunted increases in forearm NE spillover during nonhypotensive LBNP and augmented plasma epinephrine (EPI) responses. In a patient with the Shy- Drager syndrome and multiple myeloma, in vitro testing supported an autoimmune causal mechanism for the disease. Results of a collaborative study of clozapine indicated that this novel neuroleptic affects several aspects of peripheral noradrenergic function. We obtained evidence for functional stimulatory beta-adrenoceptors on sympathetic terminals in the human forearm, without evidence for functional stimulatory receptors for angiotensin II. In humans, the main identified modulator of transmitter release from sympathetic nerves appeared to be inhibitory, mediated by alpha2-adrenoceptors.