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

• Published in: Biochemical and biophysical research communications Vol. 151; no. 2; p. 897
• Main Authors: Buckman, T D, Chang, R, Sutphin, M S, Eiduson, S
• Format: Journal Article
• Language: English
• Published: United States 15-03-1988
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 1-Methyl-4-phenylpyridinium; Adenosine Triphosphate - blood; Biological Transport; Blood Platelets - metabolism; Humans; Kinetics; Neurotoxins - blood; Pyridines - blood; Pyridinium Compounds - blood; Rotenone - pharmacology; Serotonin Antagonists - pharmacology
• ISSN: 0006-291X
• DOI: 10.1016/S0006-291X(88)80366-8

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.