Interaction of 1-methyl-4-phenylpyridinium ion and tyramine with a site putatively involved in the striatal vesicular release of dopamine.
The neurotoxin MPP+ potently inhibited the striatal binding of [3H]-tyramine, a putative marker for the vesicular transporter of dopamine, and provoked a massive in vivo release of striatal dopamine. Tetrabenazine, an established ligand for the vesicular catecholamine carrier, potently inhibited [3H]-tyramine binding, tyramine-provoked striatal efflux of dopamine and the fast component of MPP(+)-induced dopamine release. It is concluded that MPP+ in the striatum, besides interacting with additional intracellular targets, avidly binds at a vesicular site functionally involved with the outward transport of dopamine.
Vaccari
A
A
Department of Neuroscience, Cagliari, Italy.
Del Zompo
M
M
Melis
F
F
Gessa
G L
GL
Rossetti
Z L
ZL
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D066298:In Vitro Techniques; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011726:Pyridinium Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013747:Tetrabenazine / Q000494:pharmacology; D014439:Tyramine / Q000378:metabolism / Q000494:pharmacology*
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011726:Pyridinium Compounds; C026560:1-(4-methoxyphenyl)pyridinium; D004298:Dopamine; D014439:Tyramine; D013747:Tetrabenazine