Carrier‐mediated efflux of [ 3 H] dopamine and [ 3 H]1‐methyl‐4‐phenylopyridine: Effects of ascorbic acid

The carrier‐mediated efflux of [ 3 H]1‐methyl‐4‐phenylpyridine (MPP + ) and [ 3 H] dopamine was examined in mouse striatal synaposomal p 2 fractions. Although the two compound 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 [ 3 H] dopamine, externally present dopamine at concentration of 1.3 μM reduced the intrasynaprosomal concentration of [ 3 H] dopamine by 50% (the EC R value) with 8 min of incubation. The EC R value of dopamine in promoting the efflux of [ 3 H]MPP + was only 0.15 μM. Similarly [ 3 H] ascorbic acid was weaker in enhancing the efflux of dopamine (EC R > 2000 μM) than that of [ 3 H] MPP + (EC R = 567 μM). This effect of ascorbic acid on the efflux of [ 3 H]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.