Different effects of 1-methyl-4-phenyl-pyridinium (MPP+) on monoamine oxidase of dopaminergic terminals in caudate nucleus slices from pigmented and from albino rabbits.
Slices of caudate nucleus from pigmented and from albino rabbits were preincubated in vitro for 24 h with different concentrations of the neurotoxic compound MPP+. Subsequently, endogenous dopamine (DA) in the slices was determined by HPLC. MPP+ (1 and 3.2 mumol/l) was more effective in diminishing DA levels in caudate nucleus slices from albino than in slices from pigmented rabbits. Following 24 h pretreatment with MPP+, the accumulation of [3H]-DA in caudate nucleus slices from pigmented rabbits was either enhanced (at 0.32 mumol/l, 1 mumol/l and 3.2 mumol/l MPP+) or reduced (at 32 mumol/l MPP+). In contrast, MPP+ did not enhance the accumulation of [3H]-DA in caudate nucleus tissue from albino rabbits and was more potent in reducing the [3H]-DA content in slices from albino than in slices from pigmented rabbits. When the selective type A monoamine oxidase (MAO) inhibitor clorgyline was present during pre-incubation, but not when the selective type B MAO inhibitor deprenyl was, the concentration-response curve for MPP+ with caudate nucleus slices from pigmented rabbits was similar to that obtained with slices from albino rabbits. Clorgyline and deprenyl did not change the effects of MPP+ in caudate nucleus slices from albino rabbits. These findings are compatible with the hypothesis that the MAO within dopaminergic terminals in the caudate nucleus of pigmented, but not of albino, rabbits is of type A since MAO-A is preferentially inhibited by MPP+. In line with this hypothesis, the accumulation of the preferential MAO-A substrate [3H]-5-HT in caudate nucleus slices from pigmented rabbits was about 39% lower than that in slices from albino rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)
Lupp
A
A
Neuropharmakologisches Labor, Neurologischen Universitätsklinik, Freiburg, Federal Republic of Germany.
Lücking
C H
CH
Hedler
L
L
Feuerstein
T J
TJ
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D003010:Clorgyline / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism* / Q000493:pharmacokinetics; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008543:Melanins / Q000502:physiology; D008995:Monoamine Oxidase / Q000187:drug effects*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009411:Nerve Endings / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D010858:Pigmentation / Q000502:physiology*; D011817:Rabbits; D012642:Selegiline / Q000494:pharmacology; D012701:Serotonin / Q000493:pharmacokinetics; D014316:Tritium
D008543:Melanins; D008996:Monoamine Oxidase Inhibitors; D014316:Tritium; D012642:Selegiline; D012701:Serotonin; D008995:Monoamine Oxidase; D003010:Clorgyline; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine