N-G-NITRO-L-ARGININE METHYL-ESTER MODULATES INTESTINAL SECRETION AND MOTILITY PRODUCED BY CARBACHOL

The effects of the nitric oxide (NO) synthesis inhibitor, N-G-nitro-L-arginine methyl ester, on carbachol-induced diarrhoea, fluid accumulation and motility changes were studied. Pretreatment of mice with N-G-nitro-L-arginine methyl ester (1-25 mg/kg i.p.) and N-G-nitro-L-arginine (2.5-50 mg/kg i.p.) but not N-G-nitro-D-arginine methyl ester (25 mg/kg i.p.) prevented in a dose-related manner the carbachol (0.5 mg/kg i.p.)-induced diarrhoea in mice. L-Arginine (150-1500 mg/kg i.p.) administered to mice pretreated with N-G-nitro-L-arginine methyl ester counteracted the antidiarrhoeal activity of N-G-nitro-L-arginine methyl ester in a dose-related manner. Pretreatment of rats with N-G-nitro-L-arginine methyl ester (2.5-25 mg/kg i.p.) decreased the intestinal fluid accumulation induced by carbachol in rats. N-G-Nitro-D-arginine methyl ester was without effect. Intraperitoneal pretreatment of rats with N-G-nitro-L-arginine methyl ester (2.5-25 mg/kg) reduced the increase in small intestinal transit induced by carbachol. N-G-nitro-L-arginine methyl ester had no effect. These results provide evidence that nitric oxide may play a role in diarrhoea, intraluminal fluid accumulation and motility changes induced by carbachol.