NG-nitro-L-arginine methyl ester modulates intestinal secretion and motility produced by carbachol.
The effects of the nitric oxide (NO) synthesis inhibitor, NG-nitro-L-arginine methyl ester, on carbachol-induced diarrhoea, fluid accumulation and motility changes were studied. Pretreatment of mice with NG-nitro-L-arginine methyl ester (1-25 mg/kg i.p.) and NG-nitro-L-arginine (2.5-50 mg/kg i.p.) but not NG-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 NG-nitro-L-arginine methyl ester counteracted the antidiarrhoeal activity of NG-nitro-L-arginine methyl ester in a dose-related manner. Pretreatment of rats with NG-nitro-L-arginine methyl ester (2.5-25 mg/kg i.p.) decreased the intestinal fluid accumulation induced by carbachol in rats. NG-Nitro-D-arginine methyl ester was without effect. Intraperitoneal pretreatment of rats with NG-nitro-L-arginine methyl ester (2.5-25 mg/kg) reduced the increase in small intestinal transit induced by carbachol. NG-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.
Izzo
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Department of Experimental Pharmacology, University of Naples, Federico II Italy.
Mascolo
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Di Carlo
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Capasso
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D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001826:Body Fluids / Q000187:drug effects; D002217:Carbachol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005772:Gastrointestinal Transit / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
D009569:Nitric Oxide; D002217:Carbachol; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester