Nitric oxide stimulates intestinal ion transport via the activation of enteric nerves, but it is not known whether it regulates intestinal transport function by acting on the epithelium directly. The aim of this study was to determine the influence of nitric oxide on epithelial electrogenic ion secretion, measured as the short-circuit current (Isc), using the human colonic carcinoma cell line Caco-2. The cellular mechanisms were examined by measuring epithelial cGMP production, and nitrite release was monitored as an index of nitric oxide synthesized. The nitric oxide substrate L-arginine methyl ester increased nitrite release, electrogenic secretion and cell cGMP production. Pretreatment with L-NAME (Nω-nitro-L-arginine methyl ester, 1 mM), but not the D-isomer, significantly reduced the electrogenic secretion and cGMP production evoked by L-arginine methyl ester, implicating nitric oxide synthase involvement. Pretreatment with cystamine, but not Methylene Blue, significantly reduced the maximum Isc and the cGMP release induced by L-arginine methyl ester and the nitric oxide donor sodium nitroprusside, implicating the involvement of particulate guanylate cyclase. In conclusion, nitric oxide stimulates electrogenic ion secretion and cGMP production in intestinal epithelial cells by activating particulate guanylate cyclase. The direct action of nitric oxide on the intestinal epithelium may be important in the regulation of intestinal transport function in health and in inflammatory bowel disease.
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February 1999
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Research Article|
February 01 1999
Nitric oxide stimulates cyclic guanosine monophosphate production and electrogenic secretion in Caco-2 colonocytes
V. E. ROLFE;
1Gastroenterology Unit, Department of Paediatric Surgery, Institute of Child Health, 30 Guilford Street, University College London WC1N 1EH, U.K.
Correspondence: Dr Vivien Rolfe, Waltham Centre for Pet Nutrition, Freeby Lane, Waltham-on-the-Wolds, Melton Mowbray, Leicestershire LE14 4RT, U.K.
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P. J. MILLA
P. J. MILLA
1Gastroenterology Unit, Department of Paediatric Surgery, Institute of Child Health, 30 Guilford Street, University College London WC1N 1EH, U.K.
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Publisher: Portland Press Ltd
Received:
July 06 1998
Revision Received:
October 05 1998
Accepted:
October 09 1998
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 1999
1999
Clin Sci (Lond) (1999) 96 (2): 165–170.
Article history
Received:
July 06 1998
Revision Received:
October 05 1998
Accepted:
October 09 1998
Citation
V. E. ROLFE, P. J. MILLA; Nitric oxide stimulates cyclic guanosine monophosphate production and electrogenic secretion in Caco-2 colonocytes. Clin Sci (Lond) 1 February 1999; 96 (2): 165–170. doi: https://doi.org/10.1042/cs0960165
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