Consequences of monoamine oxidase inhibition: increased vesicular accumulation of dopamine and norepinephrine and increased metabolism by catechol-O-methyltransferase and phenolsulfotransferase.
1. Male Sprague-Dawley rats were injected with saline, L-Dopa or pargyline. 2. Synaptic vesicles were prepared from whole brain homogenates. Catecholamines and their metabolites in brain tissues and in synaptic vesicles were measured by high performance liquid chromatography with electrochemical detection. 3. L-Dopa administration raised brain dopamine markedly but did not significantly change dopamine and norepinephrine in the vesicular fraction. 4. The dopamine increase following L-Dopa was not accompanied by any change in normetanephrine, 3-methoxytyramine or dopamine sulfate. 5. In comparison to the control rats and rats injected with L-Dopa, pargyline-treated rats exhibited significantly higher vesicular norepinephrine and dopamine. 6. The dopamine and norepinephrine increases following pargyline treatment were accompanied by significant increases in 3-methoxytyramine, normetanephrine and dopamine sulfate. 7. The increases in vesicular dopamine and norepinephrine may be the origin of their increased metabolism by extraneuronal enzymes, catechol-O-methyltransferase and phenolsulfotransferase.
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Laboratory of the Autonomic Nervous System, Institut de Recherches Cliniques de Montreal, Qc, Canada.
Lussier
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D000818:Animals; D015239:Arylsulfotransferase / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010293:Pargyline / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism
D007980:Levodopa; D010293:Pargyline; D002394:Catechol O-Methyltransferase; D015239:Arylsulfotransferase; D004298:Dopamine; D009638:Norepinephrine