Interaction of 1-methyl-4-phenylpyridinium ion with human platelets.

When uptake of the Parkinson's syndrome inducing neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and its major brain metabolite MPP+ (1-methyl-4-phenylpyridinium ion) by human platelets were compared in platelet rich plasma, a much higher rate was observed for the metabolite. The uptake process was saturable (Km = 6.8 microM; Vmax = 0.064 nmole/min/mg protein) and could be blocked by inhibitors of serotonin uptake. The accumulation of MPP+ by the platelets was accompanied by a decrease in intracellular ATP and an inhibition of mitochondrial state 3 respiration. These findings are consistent with earlier reports of the effect of MPP+ on isolated mitochondria as a potential cytotoxic mechanism, but also demonstrate that the dopamine uptake system is not the only means by which this metabolite can be efficiently transported into cells.