The role of nitric oxide in the kainate-induced seizures in mice.
The effect of L-arginine (L-Arg), D-arginine (D-Arg), N-nitro-L-arginine methyl ester (L-NAME) and N-monomethyl-L-arginine (L-NMMA) on the kainate-induced seizures was studied in mice. It was found that the precursor of nitric oxide (NO) L-Arg (150-600 mg/kg i.p.) increased dose-dependently the dose of kinate necessary to produce clonic convulsions in 50% of the animals (CD50). Such an anticonvulsant effect was not observed in mice pretreated with D-Arg (150-600 mg/kg i.p.), the latter drug not being a substrate for NO formation. The inhibitors of NO synthase L-NAME and L-NMMA, both administered in doses of 30-30 mg/kg i.p., reduced the convulsive threshold by decreasing the CD50 of kainate. Moreover, L-NAME (3 mg/kg) antagonized the anticonvulsant effect of L-Arg (300 mg/kg). These results indicate that NO may play a role of an endogenous anticonvulsant substance in mice.
Przegaliński
E
E
Institute of Pharmacology Polish Academy of Sciences, Kraków, Poland.
Baran
L
L
Siwanowicz
J
J
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007608:Kainic Acid; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D007608:Kainic Acid; D019331:NG-Nitroarginine Methyl Ester