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 [3H]MPP+ but not [3H]dopamine was dose-dependently inhibited by cocaine and other compounds known as dopamine uptake inhibitor, 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)-piperazine (GBR12,935) and nomifensine, although the uptake of both [3H]dopamine and [3H]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.
Kitayama
S
S
Department of Pharmacology, Hiroshima University School of Dentistry, Japan.
Morita
K
K
Dohi
T
T
D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D004305:Dose-Response Relationship, Drug; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D051381:Rats
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D003042:Cocaine; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine