The mechanism of action of MPTP and MPP+ on endogenous dopamine release from the rat corpus striatum superfused in vitro.
In this paper, using an in vitro superfusion system, we examined in the rat corpus striatum (CS) the action of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and N-methylphenylpyridine (MPP+) on dopamine (DA) metabolism. MPTP, at at 10(-5) M and 10(-4) M, caused decreases in 3,4-dihydroxyphenylacetic acid (DOPAC) output in a dose-dependent manner. In addition, at 10(-4) M, MPTP caused an increase in DA release from CS. On the other hand, at 10(-6) M and 10(-5) M, MPP+ exerted very potent and rapid inhibition on DOPAC output and stimulated DA release in a dose-dependent manner. Furthermore, pretreatment of MPP+ markedly potentiated K+-stimulated DA release from CS. From the present data, we propose that MPP+ (the active metabolite of MPTP) inhibits DA reuptake system and/or monoamine oxidase (MAO) activity, increases readily releasable pool of DA and stimulates DA release from dopaminergic terminals.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D008297:Male; D010477:Perfusion; D011188:Potassium / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011725:Pyridines; D011726:Pyridinium Compounds; D015102:3,4-Dihydroxyphenylacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D011188:Potassium; D004298:Dopamine