Evidence for the involvement of L-citrulline but not nitric oxide in the proconvulsant action of the precursor L-arginine on picrotoxin-induced convulsions in rats.
To determine the role of the metabolites of L-arginine in its actions on picrotoxin-induced convulsions in rats, the concentrations of nitric oxide (NO) and L-citrulline were measured in the brain 30 and 60 min after the administration of L-arginine (1000 and 2000 mg/kg) or of N-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg), an inhibitor of NO synthase. Animals treated similarly were challenged 30 and 60 min later with picrotoxin (5mg/kg), and the time of onset of myoclonus and clonic convulsions and the frequency of convulsions were determined. These parameters were also determined 30 and 60 min after administering L-arginine in L-NAME-pretreated (30 min) animals. Thirty minutes after the administration of L-arginine, the concentrations of both NO and L-citrulline were raised, the onset of myoclonus and clonic convulsions was delayed, and the frequency of convulsions was decreased, indicating the anticonvulsant property of L-arginine. A 60-min treatment of L-arginine produced a further increase in the concentration of L-citrulline but not that of NO and promoted the frequency of picrotoxin-induced convulsions. Pretreatment with L-NAME prevented L-arginine from raising the concentrations of both NO and L-citrulline; it also promoted the anticonvulsant actions and prevented the proconvulsant actions of L-arginine. These results lead to the conclusion that NO has no involvement in the time-dependent anti and proconvulsant actions of L-arginine on the picrotoxin convulsion model, and that L-citrulline seems to have a role in the proconvulsant action of L-arginine.
Paul
Vanaja
V
Department of Pharmacology and Environmental Toxicology, Dr. A.L.M. Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani, 600 113, Chennai, India. pgibms@md2.vsnl.net.in
D000818:Animals; D001120:Arginine / Q000502:physiology*; D002956:Citrulline / Q000378:metabolism*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine