首页> 中文期刊> 《中国药理学报:英文版》 >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

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

         

摘要

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2.5 Hz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(2 mg/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.%AIM: 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-enzynatic assay. RESULTS: Fxogenous 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 transporation 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 DOMAconcentrations 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-synapfic reuptake plus oxidative deamination on the external membrane of mitochodria, is predominant for the reduction to DHPG.

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