Cocaine inhibits the release of MPP(+) but not dopamine through the rat dopamine transporter

Transporter-mediated release of dopamine and the parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) was examined in COS cells, a cell line derived from monkey kidney, expressing the rat dopamine transporter. The release of preloaded [H-3]MPP(+) but not [H-3]dopamine was dose-dependently inhibited by cocaine and other compounds known as dopamine uptake inhibitor, 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)-piperazine (GBR12935) and nomifensine, although the uptake of both [H-3]dopamine and [H-3]MPP(+) was sensitive to these compounds. The different sensitivity of the outward transport of dopamine and MPP(+) to the uptake inhibitors might provide a clue to the identity of the specific site(s) for cocaine on the transporter.