Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its toxic metabolites on the physicochemical property of the liposomal membrane in relation to their cytochrome P-450 inhibition.
The effects of the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and its toxic metabolites MPDP+ (1-methyl-4-phenyl-2,3-dihydropyridinium) and MPP+ (1-methyl-4-phenylpyridinium) on liposomal membrane were assessed using fluorescence-polarization and carboxyfluorescein leakage studies as well as in biological membrane preparations. Of the three compounds, MPTP was found to cause the greatest perturbation of membrane followed by MPDP+ and then MPP+. The ability of the three toxins to inhibit cytochrome P-450 enzyme activity (a microsomal membrane-bound enzyme system) was also studied and their relative potency was again found to be MPTP > MPDP+ > MPP+. The changes in the physicochemical property of the liposomal membrane can be related to the ability of the neurotoxin's ability to inhibit cytochrome P-450 activity.
Das
N P
NP
Department of Biochemistry, National University of Singapore.
Shahi
G S
GS
Moochhala
S M
SM
Sato
T
T
Sunamoto
J
J
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D019363:Cytochrome P-450 CYP1A1; D065607:Cytochrome P-450 Enzyme Inhibitors; D004134:Dimyristoylphosphatidylcholine; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007700:Kinetics; D008081:Liposomes; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000378:metabolism*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence
D065607:Cytochrome P-450 Enzyme Inhibitors; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008081:Liposomes; D011726:Pyridinium Compounds; C024098:6-carboxyfluorescein; C044755:1-methyl-4-phenyl-2,3-dihydropyridinium; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D015655:1-Methyl-4-phenylpyridinium; D004134:Dimyristoylphosphatidylcholine