Norepinephrine metabolism in neuron: dissociation between 3,4-dihydroxyphenylglycol and 3,4-dihydroxymandelic acid pathways.
Abstract
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-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
mitochondria, is predominant for the reduction to DHPG.
Keywords:
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
mitochondria, is predominant for the reduction to DHPG.