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Rat Brain Norepinephrine Metabolism: Substantial Clearance Through 3,4‐Dihydroxyphenylethyleneglycol Formation
Author(s) -
Li Peter P.,
Warsh Jerry J.,
Godse Damodar D.
Publication year - 1983
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1983.tb09052.x
Subject(s) - norepinephrine , metabolism , chemistry , neuroscience , brain chemistry , endocrinology , medicine , biology , dopamine
To assess whether the metabolic clearance of rat brain norepinephrine (NE) through 3,4‐dihydroxyphenylethyleneglycol (DHPG) formation is quantitatively comparable or greater than through 3‐methoxy‐4‐hydroxyphenylethyleneglycol (MHPG) production, we studied the accumulation rates of conjugated DHPG and MHPG following probenecid administration in whole brain as well as in several brain regions. Administration of increasing doses of probenecid (100–500 mg/kg, i.p .) 1.5 h before sacrifice produced a dose‐dependent increase of conjugated DHPG and MHPG levels. The maximum increment of these conjugated metabolites occurred at a dose of 300 mg/kg or higher. During the first hour following probenecid administration (300 mg/kg, i.p.), rat brain conjugated DHPG and MHPG levels accumulated linearly at a rate of 646 and 319 pmol/g/h, respectively. With the probenecid technique, the estimated appearance rates of conjugated DHPG significantly exceeded those of conjugated MHPG in hypothalamus, midbrain, brainstem, hippocampus, and cerebral cortex. These results clearly indicate that under resting conditions, formation and efflux of conjugated DHPG is the major route of metabolic clearance of rat brain NE.