Norepinephrine metabolism in neuron: dissociation between 3, 4-dihydroxyphenylglycol and 3,4-dihydroxymandelic acid pathways  

神经元内去甲肾上腺素的代谢:3,4-二羟苯乙醇和3,4-二羟苯乙酸两条途径分离(英文)

作　　者：董文心[1] 倪湘莲[1] 

机构地区：[1]上海医药工业研究院药理研究室,上海中国200437

出　　处：《Acta Pharmacologica Sinica》2002年第1期61-67,共7页中国药理学报（英文版）

摘　　要：To investigate the pre-synaptic metabolism of norepinephrine ( NE), judged by variations in plasma concentration of 3,4-dihydroxyphenylglycol (DHPG) and 3,4-dihydroxymandelic acid (DOMA). METHODS: Pithed and electrically stimulated (2.5 Hz) rats were given intravenous infusion of exogenous NE (6 nmol·kg-1·min-1). Plasma NE, DHPG, DOMA, and the activities of mono-amine oxidases (MAO) were measured with the radio-enzymatic assay. RESULTS: Exogenous NE induces an about 100-fold increase in plasma NE concentration while blood pressure remained within normal limits. A 12-fold increase in plasma DHPG and 1.2-fold increase for DOMA were observed. When NE transportation across the pre-synaptic membrane was inhibited by desipramine (2 mg/kg, iv ), a great reduction in plasma DHPG concentration (about 25 % of control) was observed while DOMA remained unchanged. When MAO-A activity was inhibited to 25 % of control by clorgyline (2 mg/kg, iv) and MAO-B to 30 % by deprenyl, the plasma DHPG and DOMA concentrations were reduced to 15 % and 70 % of controls, and to 26 % and 76 % of controls, respectively. When clorgyline and deprenyl were combined, plasma DHPG was vanished (less than 2 % of control) while plasma DOMA remained in the same range (72 % of control). CONCLUSION: The metabolizing system of NE in pre-synapse, associating with the pre-synaptic reuptake plus oxidative deamination on the external membrane of mitochodria, is predominant for the reduction to DHPG.目的:以血浆3,4-二羟苯乙醇(DHPG)和3,4-二羟苯乙酸(DOMA)的变化为判断指标,研究去甲肾上腺素(NE)在神经元内的代谢.方法:大鼠去脊髓并给予2.5Hz电刺激合并静脉内输入NE(6 nmol·kg^(-1)·min^(-1)).同位素酶标法测定血浆DHPG和DOMA浓度.结果:当静脉内输入NE使血浆NE浓度增加了100倍时,血浆DHPG和DOMA分别增加了12倍和1.2倍.地昔帕明(2mg/kg iv)使血浆DHPG浓度降低为对照组的25％,而DOMA无明显变化.MAO-A抑制剂氯吉林使血浆DHPG和DOMA浓度分别降低为对照组的15％和70％,MAO-B抑制剂司立吉林使二者的血浆浓度分别降低为对照组的26％和76％.氯吉林与司立吉林合用使血浆DHPG几乎完全消失,而DOMA无明显变化.结论:去甲肾上腺素被突触前膜摄取后,经线粒体外膜上的MAO氧化脱胺、还原产生DHPG为其主要代谢途径.

关 键 词：norepinephnne METABOLISM mono-amine oxidase DESIPRAMINE DEPRENYL CLORGYLINE 

分 类 号：R96[医药卫生—药理学]