L-Deprenyl prevents the cell hypoxia induced by dopaminergic neurotoxins, MPP(+) and beta-carbolinium: a microdialysis study in rats.
N-Methyl-4-phenylpyridinium (MPP(+)) and 2,9-di-methyl-norharmanium (2,9-Me2NH(+)), which is a beta-carbolinium proposed as an endogenous MPP(+)-like toxin underlying Parkinson's disease, are strong mitochondrial toxins. We have measured the extracellular lactate levels as a marker for the in vivo cell hypoxia in the striatum of freely moving rats. The perfusions with MPP(+) and 2,9-Me2NH(+) increased extracellular lactate levels in a dose-dependent manner. These increases in lactate levels were significantly prevented by the co-perfusion with 10 microM L-deprenyl, a selective monoamine oxidase (MAO)-B inhibitor, but not by pargyline, a non-specific MAO inhibitor. The increase in extracellular lactate levels was considered to be the reflection of the cell damage resulted from the impairment of mitochondrial function. The present results suggested that L-deprenyl would rescue nerve cells from these toxins through the direct influence on the mitochondrial electron transport.
Matsubara
K
K
Department of Hospital Pharmacy and Pharmacology, Asahikawa Medical College, Asahikawa, 078-8510, Japan. kmatsuba@asahikawa-med.ac.jp
Senda
T
T
Uezono
T
T
Awaya
T
T
Ogawa
S
S
Chiba
K
K
Shimizu
K
K
Hayase
N
N
Kimura
K
K
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D002243:Carbolines / Q000633:toxicity*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity*; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D010293:Pargyline / Q000494:pharmacology; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012642:Selegiline / Q000494:pharmacology*
D002243:Carbolines; D006540:Herbicides; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D009498:Neurotoxins; D012642:Selegiline; D019344:Lactic Acid; C005986:2,9-dimethyl-beta-carbolinium; D010293:Pargyline; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine