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

Abstract

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 (5 mg/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.