Potentiation by reserpine and tetrabenazine of brain catecholamine depletions by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in the mouse; evidence for subcellular sequestration as basis for cellular resistance to the toxicant.
Administration to mice of the neurotoxicant MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) decreased striatal dopamine and, to a lesser extent, hippocampal noradrenaline levels when measured 2 weeks after the last dose of MPTP. Reserpine and tetrabenazine, inhibitors of catecholamine vesicular transporter, potentiated the catecholamine depletions produced by MPTP in the hippocampus and striatum, respectively. These results are compatible with our hypothesis that sequestration of the toxic MPTP metabolite MPP+ (1-methyl-4-phenylpyridinium) in the catecholamine storage vesicle retards the catecholaminergic toxicity of MPTP.
Reinhard
J F
JF
Department of Medicinal Biochemistry, Wellcome Research Laboratories, Research Triangle Park, NC 27709.
Daniels
A J
AJ
Viveros
O H
OH
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004347:Drug Interactions; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism / Q000633:toxicity*; D012110:Reserpine / Q000494:pharmacology*; D013347:Subcellular Fractions; D013747:Tetrabenazine / Q000494:pharmacology*
D002395:Catecholamines; D011725:Pyridines; D012110:Reserpine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D009638:Norepinephrine; D013747:Tetrabenazine