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.
Buckman
T D
TD
Department of Psychiatry and Biobehavioral Sciences Medical School, University of California, Los Angeles 90024.
Chang
R
R
Sutphin
M S
MS
Eiduson
S
S
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D000255:Adenosine Triphosphate / Q000097:blood; D001692:Biological Transport; D001792:Blood Platelets / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009498:Neurotoxins / Q000097:blood*; D011725:Pyridines / Q000097:blood*; D011726:Pyridinium Compounds / Q000097:blood*; D012402:Rotenone / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology
D009498:Neurotoxins; D011725:Pyridines; D011726:Pyridinium Compounds; D012702:Serotonin Antagonists; D012402:Rotenone; D000255:Adenosine Triphosphate; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium