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


CONCLUSIONS
The metabolizing system of NE in pre-synapse, associating with the pre-synaptic reuptake plus oxidative deamination on the external membrane of mitochondria, is predominant for the reduction to DHPG.
Dong
Wen-Xin
WX
Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China. dwxslgk@online.sh.cn
Ni
Xiang-Lian
XL
D000818:Animals; D003010:Clorgyline / Q000494:pharmacology; D002818:Cordotomy; D003891:Desipramine / Q000494:pharmacology; D004558:Electric Stimulation; D008297:Male; D008333:Mandelic Acids / Q000097:blood*; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000097:blood*; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats
D008333:Mandelic Acids; D008996:Monoamine Oxidase Inhibitors; D008734:Methoxyhydroxyphenylglycol; C000989:3,4-dihydroxymandelic acid; D008995:Monoamine Oxidase; D003010:Clorgyline; D003891:Desipramine; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine