Carrier-mediated efflux of [3H]dopamine and [3H]1-methyl-4-phenylpyridine: effect of ascorbic acid.
The carrier-mediated efflux of [3H]1-methyl-4-phenylpyridine (MPP+) and [3H]dopamine was examined in mouse striatal synaptosomal P2 fractions. Although the two compounds are transported by the same carrier, the translocation of the carrier-ligand complex is more rapid with MPP+ than with dopamine. With dopamine-stimulated efflux of preloaded [3H]dopamine, externally present dopamine at a concentration of 1.3 microM reduced the intrasynaptosomal concentration of [3H]dopamine by 50% (the ECR value) with 8 min of incubation. The ECR value of dopamine in promoting the efflux of [3H]MPP+, however, was only 0.15 microM. Similarly, ascorbic acid was weaker in enhancing the efflux of [3H]dopamine (ECR greater than 2000 microM) than that of [3H]MPP+ (ECR = 567 microM). This effect of ascorbic acid on the efflux of [3H]MPP+ was attenuated by mazindol, a blocker of dopamine uptake. It is proposed that ascorbic acid has a neuromodulatory role involving changes at the level of carrier-membrane translocation and/or orientation.
Debler
E A
EA
Nathan S. Kline Institute for Psychiatric Research, Center for Neurochemistry, Ward's Island, New York, New York 10035.
Sershen
H
H
Hashim
A
A
Lajtha
A
A
Reith
M E
ME
D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism*; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004058:Diffusion; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008995:Monoamine Oxidase / Q000378:metabolism; D010293:Pargyline / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism
D012110:Reserpine; D010293:Pargyline; D008995:Monoamine Oxidase; D001205:Ascorbic Acid; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine