Nitric oxide donating compounds stimulate human colonic ion transport in vitro.

W A Stack, B Filipowicz, C J Hawkey

Division of Gastroenterology, University Hospital, Queens Medical Centre, Nottingham.

BACKGROUND: Nitric oxide (NO) has been recently implicated as a possible mediator of bowel inflammation and has also been shown to stimulate electrogenic chloride secretion in rat and guinea pig intestine. This study therefore investigated the effect on two NO donors, sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) on human colonic ion transport. METHODS: Changes in short circuit current (delta SCC) in response to nitric oxide donating compounds were measured in muscle stripped normal human colon mounted in Ussing chambers. The ion species and intracellular mechanisms responsible for delta SCC evoked by SNP were investigated. RESULTS: Basolateral SNP caused a progressive rise in delta SCC over the range 10(-7) to 10(-4)M (ED50 = 2.5 x 10(-5)M). SNAP 10(-4)M also evoked a qualitatively similar delta SCC compared with SNP 10(-4)M. Basolateral SNP evoked a greater delta SCC than apical and this was significantly attenuated by bumetanide 10(-4)M (52.9 +/- 10.1%) and in chloride free media (68.3 +/- 7.3%). delta SCC response to SNP was not significantly changed by basolateral 4-acetamido-4'-isothio-cyano-2,2'disulphonic acid stillbene (SITS 10(-3)M) an inhibitor of sodium/bicarbonate exchange, or apical amiloride 10(-5)M an inhibitor of sodium absorption. SNP induced delta SCC was also significantly reduced by piroxicam (mean (SEM)) 10(-5)M (57.9 (11.9)%), nordihydroguaretic acid 10(-4)M (48.0 (12.9)%), tetrodotoxin (TTX 10(-6)M, 52.3 (9.1)%), and practically abolished by TTX and piroxicam together (96.8 (3.3)%). CONCLUSION: NO donors stimulate human colonic ion transport in vitro. For SNP, increased delta SCC is at least due in part to chloride secretion, and the response seems to be transduced through enteric nerves and by local prostanoid synthesis. This study provides evidence that NO may be another important mediator of ion transport in human colon.

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