title: The mechanism of action of MPTP and MPP+ on endogenous dopamine release from the rat corpus striatum superfused in vitro.
abstract: 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.
mesh_terms: 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
chemical_list: 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