Possible involvement of nitric oxide in quinolinic acid-induced convulsion in mice

Pharmacol Biochem Behav. 1995 Jun-Jul;51(2-3):309-12. doi: 10.1016/0091-3057(94)00385-v.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate* / analogs & derivatives*
  • Amino Acids / pharmacology
  • Animals
  • Anticonvulsants / pharmacology
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Biopterins / analogs & derivatives
  • Biopterins / pharmacology
  • Dizocilpine Maleate / pharmacology
  • Dose-Response Relationship, Drug
  • Injections, Intraventricular
  • Kynurenic Acid / analogs & derivatives
  • Kynurenic Acid / pharmacology
  • Male
  • Mice
  • Mice, Inbred Strains
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / physiology*
  • Nitroprusside / pharmacology
  • Piperazines / pharmacology
  • Quinolinic Acid* / administration & dosage
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Seizures / chemically induced
  • Seizures / physiopathology*
  • omega-N-Methylarginine

Substances

  • Amino Acids
  • Anticonvulsants
  • Piperazines
  • Receptors, N-Methyl-D-Aspartate
  • Nitroprusside
  • Biopterins
  • omega-N-Methylarginine
  • Nitric Oxide
  • Dizocilpine Maleate
  • 2-Amino-5-phosphonovalerate
  • Arginine
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
  • sapropterin
  • Quinolinic Acid
  • Kynurenic Acid
  • 2-amino-7-phosphonoheptanoic acid
  • 7-chlorokynurenic acid