Enhancement by tetraphenylboron of the interaction of the 1-methyl-4-phenylpyridinium ion (MPP+) with mitochondria.
Inhibition of mitochondrial energy production by MPP+ may be the key step in chemically-induced Parkinson's disease. Tetraphenylboron (TPB-) markedly enhances the effect of MPP+. Inhibition of respiration and uptake of MPP+ are accelerated, the former by up to two orders of magnitude. TPB increases the final concentration of MPP+ in the matrix by 2-3 fold, insufficient to explain the rapid inhibition of respiration. TPB- lowers the membrane surface potential by only about 20%, but increases the partitioning of MPP+ into organic solvent by one order of magnitude. TPB- also enhances the effect of MPP+ on inverted membranes, reducing the I50 by an order of magnitude. We suggest that TPB- acts by ion pairing with MPP+ to facilitate penetration into mitochondria as well as access to a hydrophobic inhibition site on NADH dehydrogenase.
Ramsay
R R
RR
Department of Biochemistry-Biophysics, University of California, San Francisco 94143.
Mehlhorn
R J
RJ
Singer
T P
TP
D015655:1-Methyl-4-phenylpyridinium; D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology*; D004579:Electron Transport; D007700:Kinetics; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D011726:Pyridinium Compounds / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013775:Tetraphenylborate / Q000494:pharmacology*
D001896:Boron Compounds; D009498:Neurotoxins; D011726:Pyridinium Compounds; D013775:Tetraphenylborate; D015655:1-Methyl-4-phenylpyridinium