Transporter

The uptake and cytotoxicity of 1-methyl-4-phenylpyridinium (MPP), the toxic metabolite of the parkinsonism inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), were studied in COS-7 cells transiently transfected with the cloned human noradrenaline and dopamine transporters and in permanently transfected SK-N-MC neuroblastoma cells. MPP had a 1 0- to 20-fold lower Km value for the noradrenaline than for the dopamine transporter. In dopamine transporter express-ing cells, the maximal transport rate (Vma)3 of MPP, dopamine and noradrenaline was the same, but in noradrenaline trans-porter expressing cells the Vmas of MPP and dopamine was only one-half of the Vm of noradrenaline. The turnover num-bers (VmHE of uptake/maximal binding sites of binding) were 5 times higher for the dopamine transporter (as measured with [3H]dopamine and [3H]-2f3-carbomethoxy-33-(4-fluorophenyl