Modification of vesicular dopamine and norepinephrine by monoamine oxidase inhibitors.
The possible effects of inhibitors of the two forms of monoamine oxidase (types A and B) on dopamine (DA) and norepinephrine (NE) accumulation and metabolism in the cytoplasmic and microsomal (vesicular) fractions of the rat brain have been examined. It was found that, while L-DOPA treatment raised only cytoplasmic DA without affecting vesicular DA and NE, clorgyline and pargyline treatments caused significant increases in DA and NE concentrations in both cytoplasmic and vesicular fractions. The DA increase in the synaptic vesicles (200-600%) was much more pronounced than that (150%) in the cytoplasm. In contrast, deprenyl treatment increased vesicular DA only slightly without any effect on either vesicular or cytoplasmic NE. L-DOPA administration to rats pretreated with clorgyline and pargyline, but not with deprenyl, further increased cytoplasmic and vesicular DA and NE concentrations. However, excessive increases in vesicular DA lowered vesicular NE. Reserpine drastically reduced vesicular and cytoplasmic DA and NE, and L-DOPA administration to the reserpine-treated rats caused a DA increase only in the cytoplasmic fraction without affecting vesicular DA or NE. The effect of reserpine was abolished by pargyline treatment, which suggests that pargyline may interact with the reserpine-sensitive vesicular uptake. There was a significant correlation between vesicular DA and NE increase.
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Laboratory of the Autonomic Nervous System, Clinical Research Institute of Montreal, Quebec, Canada.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D003593:Cytoplasm / Q000032:analysis; D004298:Dopamine / Q000032:analysis*; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology; D013572:Synaptic Vesicles / Q000032:analysis* / Q000187:drug effects
D008996:Monoamine Oxidase Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D012110:Reserpine; D004298:Dopamine; D009638:Norepinephrine