Quinolinic acid induces NMDA receptor-mediated lipid peroxidation in rat brain microvessels.
Quinolinic acid increased the generation of lipid peroxidation products by isolated rat brain microvessels in vitro. The effect was inhibited both by a specific NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid and by reduced glutathione (GSH). Furthermore, quinolinic acid displaced specific binding of [(3)H]-L-glutamate by cerebral microvessel membranes, particularly in the presence of NMDA receptor co-agonist (glycine) and modulator (spermidine). We conclude that quinolinic acid can cause potentially cytotoxic lipid peroxidation in brain microvessels via an NMDA receptor mediated mechanism.
Prague Psychiatric Centre affiliated with Charles University 3rd Faculty of Medicine, Prague, Czech Republic.
Frantisek
F
St'astný
Václav
V
Lisý
Vladislav
V
Mares
Vera
V
Lisá
Vladimir J
VJ
Balcar
Abel
A
Santamaría
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000502:physiology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D015763:2-Amino-5-phosphonovalerate; D005978:Glutathione