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Inhibitors of nitric oxide synthetase prevent castor‐oil‐induced diarrhoea in the rat
Author(s) -
Mascolo N.,
Izzo A.A.,
Barbato F.,
Capasso F.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13478.x
Subject(s) - castor oil , antidiarrhoeal , nitric oxide , arginine , chemistry , omega n methylarginine , pharmacology , biochemistry , nitric oxide synthase , medicine , amino acid , organic chemistry
1 Castor oil (2 ml orally) produced copious diarrhoea in rats 3 h after its administration. 2 Pretreatment (intraperitoneal, i.p.) of rats with the NO synthesis inhibitors N G ‐nitro‐ l ‐arginine methyl ester ( l ‐NAME, 1–25 mg kg −1 ) and N G ‐monomethyl‐ l ‐arginine ( l ‐NMMA, 2.5–100 mg kg −1 ) inhibited or prevented castor‐oil‐induced diarrhoea. l ‐Arginine (150–600 mg kg −1 , i.p.) administered to rats pretreated with l ‐NAME 10 mg kg −1 , drastically reduced the antidiarrhoeal activity of l ‐NAME in a dose‐related manner. d ‐Arginine (900 mg kg −1 ) did not modify the protection by l ‐NAME. 3 Pretreatment (i.p.) of rats with l ‐NAME (2.5–25 mg kg −1 ) decreased the intestinal fluid accumulation and Na + secretion induced by castor oil. l ‐Arginine (600 mg kg −1 ) but not d ‐arginine (900 mg kg −1 ) counteracted the inhibitory effect of l ‐NAME (10 mg kg −1 ). 4 l ‐NAME (10 and 25 mg kg −1 ) had no significant effect on the intestinal transit in normal rats or those given castor oil. 5 These results provide evidence that nitric oxide (NO) could play an important role in castor‐oil‐induced diarrhoea.