1-Methyl-4-phenylpyridinium and 3-nitropropionic acid diminish cortical synthesis of kynurenic acid via interference with kynurenine aminotransferases in rats.
The aim of the present study was to evaluate the effect of mitochondrial inhibitors, 1-methyl-4-phenylpyridinium (MPP(+)) and 3-nitropropionic acid (3-NPA), on the brain production of endogenous glutamate antagonist, kynurenic acid (KYNA). MPP(+) and 3-NPA dose-dependently impaired the synthesis of KYNA in rat cortical slices. Enzymatic studies revealed that MPP(+) inhibits in a concentration-dependent manner the activity of kynurenine aminotransferase II (KAT II), but not the activity of kynurenine aminotransferase I (KAT I). 3-NPA impaired the activity of both enzymes, KAT I and KAT II. Thus, MPP(+)- and 3-NPA-evoked neurotoxicity may be at least partially associated with the depletion of KYNA.
Luchowski
Piotr
P
Department of Pharmacology and Toxicology, Medical University, Jaczewskiego 8, 20-090 Lublin, Poland.
Luchowska
Elzbieta
E
Turski
Waldemar A
WA
Urbanska
Ewa M
EM
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology; D007736:Kynurenic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D009574:Nitro Compounds; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000637:Transaminases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D009574:Nitro Compounds; D011422:Propionates; D000637:Transaminases; C021481:kynurenine-oxoglutarate transaminase; D007736:Kynurenic Acid; C015392:3-nitropropionic acid; D015655:1-Methyl-4-phenylpyridinium