Ascorbic acid and striatal transport of [3H] 1-methyl-4-phenylpyridine (MPP+) and [3H] dopamine.
The inhibition of uptake of [3H] dopamine and [3H] 1-methyl-4-phenylpyridine (MPP+) was examined in mouse striatal synaptosomal preparations. Kinetic analysis indicated that ascorbic acid is a noncompetitive inhibitor of [3H] MPP+ uptake. No inhibition of [3H] dopamine uptake is observed. The dopamine uptake blockers, GBR-12909, cocaine, and mazindol strongly inhibit (IC50 less than 1 uM) both [3H] dopamine and [3H] MPP+ transport. Nicotine, its metabolites, and other tobacco alkaloids are weak inhibitors (IC50 greater than 1 mM) except 4-phenylpyridine and lobeline, which are moderate inhibitors (IC50 = 3 to 40 uM) of both [3H] dopamine and [3H] MPP+ uptake. These similarities in potencies are in agreement with the suggestion that [3H] MPP+ and [3H] dopamine are transported by the same carrier. The differences observed in the alteration of dopaminergic transport and mazindol binding by ascorbic acid suggest that ascorbic acid's effects on [3H] MPP+ transport are related to translocation and/or dissociation processes occurring subsequent to the initial binding event.
Debler
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EA
Nathan S. Kline Institute for Psychiatric Research, Center for Neurochemistry, Ward's Island, New York, NY 10035.
Hashim
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A
Lajtha
A
A
Sershen
H
H
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001692:Biological Transport; D003042:Cocaine / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D007700:Kinetics; D008454:Mazindol / Q000494:pharmacology; D051379:Mice; D009538:Nicotine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism
D010879:Piperazines; D011725:Pyridines; D009538:Nicotine; C043425:vanoxerine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008454:Mazindol; D003042:Cocaine; D001205:Ascorbic Acid; D004298:Dopamine