Possible involvement of nitric oxide in quinolinic acid-induced convulsion in mice.
Quinolinic acid (QA) induced clonic and tonic convulsions in mice when it was injected into the cerebral ventricle. Pretreatment with L-arginine (L-Arg), a substrate of nitric oxide (NO) synthase (NOS), and/or 5,6,7,8-tetrahydrobiopterin (THB), cofactor of NOS, tended to potentiate QA-induced convulsion. NG-monomethyl-L-arginine (NMMA), a competitive NOS inhibitor, diminished QA-induced convulsion. This effect of NMMA was attenuated by coadministration of L-Arg or THB. Sodium nitroprusside (SNP), which spontaneously releases NO, did not potentiate, but diminished QA-induced convulsion. These findings suggest that an endogenous NO may be involved, at least in part, in QA-induced convulsion in mice, and that an exogenous NO released from SNP may cause downregulation of N-methyl-D-aspartate (NMDA) receptor activity, and thereby prevent the excessive excitation of NMDA receptors and subsequent convulsion caused by QA.
Nakamura
T A
TA
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Japan.
Yamada
K
K
Hasegawa
T
T
Nabeshima
T
T
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001708:Biopterins / Q000031:analogs & derivatives / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D017378:Quinolinic Acid / Q000008:administration & dosage; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*; D019323:omega-N-Methylarginine
D000596:Amino Acids; D000927:Anticonvulsants; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D009599:Nitroprusside; D001708:Biopterins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D001120:Arginine; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; C003402:sapropterin; D017378:Quinolinic Acid; D007736:Kynurenic Acid; C031231:2-amino-7-phosphonoheptanoic acid; C057013:7-chlorokynurenic acid