Nitric oxide involvement in sodium choleate-induced fluid secretion and diarrhoea in rats.
Bile salt-induced diarrhoea, net water and electrolyte secretion, gastrointestinal transit and nitric oxide (NO) synthase activity were studied in rats. NG-Nitro-L-arginine methyl ester (2.5-25 mg/kg i.p.), an inhibitor of NO synthase, and dexamethasone (0.03-0.3 mg/kg i.p.), an inhibitor of the inducible isoform of NO synthase, antagonized the diarrhoeal response. The NO precursor, L-arginine and isosorbide-5-mononitrate (an NO donor), reversed the inhibitory effect of NG-nitro-L-arginine methyl ester. The bile salt-stimulated fluid secretion, transit through the gut and NO synthase all were inhibited by NG-nitro-L-arginine methyl ester (but not NG-nitro-D-arginine methyl ester). NO synthase activity also was inhibited by dexamethasone. The results are consistent with bile salt induction of epithelial cell injury and concomitant synthesis of NO, mainly through activation of the inducible form of the enzyme. We believe that in this study NO is a mediator of intestinal secretion and motility changes that enhance transit of luminal contents through the gut, resulting in diarrhoea.
Mascolo
N
N
Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy.
Gaginella
T S
TS
Izzo
A A
AA
Di Carlo
G
G
Capasso
F
F
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D019826:Cholic Acid; D002793:Cholic Acids / Q000037:antagonists & inhibitors / Q000633:toxicity*; D003907:Dexamethasone / Q000494:pharmacology; D003967:Diarrhea / Q000139:chemically induced / Q000503:physiopathology*; D004848:Epithelium / Q000378:metabolism; D005772:Gastrointestinal Transit / Q000187:drug effects; D007419:Intestinal Secretions / Q000187:drug effects / Q000502:physiology*; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase; D051381:Rats; D017208:Rats, Wistar; D014882:Water-Electrolyte Balance / Q000187:drug effects
D002793:Cholic Acids; D009569:Nitric Oxide; D003907:Dexamethasone; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019826:Cholic Acid; D019331:NG-Nitroarginine Methyl Ester