PLASMA DIHYDROXYPHENYLGLYCOL AND THE INTRANEURONAL DISPOSITION OF NOREPINEPHRINE IN HUMANS
PLASMA DIHYDROXYPHENYLGLYCOL AND THE INTRANEURONAL DISPOSITION OF NOREPINEPHRINE IN HUMANS
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DOI：
10.1172/jci113298
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发表时间：
1988-01-01
影响因子：
15.9
通讯作者：
KOPIN, IJ
中科院分区：
文献类型：
--
作者：
GOLDSTEIN, DS;EISENHOFER, G;KOPIN, IJ
我们检测了健康受试者和交感神经切除患者在仰卧位休息时、生理性（倾斜）或药物性（药物性）治疗期间交感神经递质去甲肾上腺素（NE）及其脱氨基代谢物二羟苯甘醇（DHPG）的血浆水平。（育亨宾，可乐定）的操作，已知影响交感神经介导的NE释放，在神经元摄取NE的阻滞（摄取-1）使用地昔帕明，并在静脉输注NE。健康受试者患肢DHPG平均增加10%，P < 0.05，而交感神经切除患者患肢DHPG平均减少21%，P < 0.05。结果表明，NE和DHPG的变化呈高度相关（r = 0.94）。去甲丙咪嗪预处理可抑制DHPG对育亨宾的反应，同时增强NE的反应。为了达到一个给定的增加血浆DHPG，约10倍大的增量，动脉NE需要在NE输注过程中比内源性NE释放。当可乐定明显抑制血浆NE时，血浆DHPG降至700-800 pg/ml的平台水平。结果表明：（1）人血浆DHPG主要来源于交感神经，（2）刺激NE释放时血浆DHPG的增加是由于NE被交感神经末梢摄取，随后在神经元内转化为DHPG，（3）基础状态下血浆DHPG可能主要由NE从贮液囊向轴突胞质的净渗漏决定;和（iv）在NE输注和NE释放期间，通过同时测量DHPG和NE，可以估计神经元摄取部位的NE浓度的增量。NE和DHPG的测量提供了关于交感神经功能的独特临床信息。
We examined plasma levels of the sympathetic neurotransmitter norepinephrine (NE) and its deaminated metabolite dihydroxyphenylglyol (DHPG) during supine rest in healthy human subjects and in sympathectomized patients, during physiological (tilt) or pharmacological (yohimbine, clonidine) manipulations known to affect sympathetically mediated NE release, during blockade of neuronal uptake of NE (uptake-1) using desipramine, and during intravenous infusion of NE. Healthy subjects had a mean arteriovenous increment in plasma DHPG in the arm (10%,P < 0.05), whereas sympathectomized patients had a mean arteriovenous decrement in DHPG in the affected limb (mean decrease 21%, P < 0.05 compared with healthy subjects). Tilt and yohimbine, which stimulate, and clonidine, which inhibits, release of endogenous NE, produced highly correlated changes in plasma NE and DHPG (r = 0.94). Pretreatment with desipramine abolished DHPG responses to yohimbine while enhancing NE responses. To attain a given increase in plasma DHPG, about a tenfold larger increment in arterial NE was required during NE infusion than during release of endogenous NE. When plasma NE was markedly suppressed after administration of clonidine, plasma DHPG decreased to a plateau level of 700-800 pg/ml. The results indicate that (i) plasma DHPG in humans is derived mainly from sympathetic nerves; (ii) increments in plasma DHPG during stimulation of NE release result from uptake of NE into sympathetic nerve endings and subsequent intraneuronal conversion to DHPG; (iii) plasma DHPG under basal conditions probably is determined mainly by net leakage of NE into the axonal cytoplasm from storage vesicles; and (iv) increments in NE concentrations at neuronal uptake sites can be estimated by simultaneous measurements of DHPG and NE during NE infusion and NE release. Measurement of NE and DHPG provides unique clinical information about sympathetic function.