{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T01:09:36Z","timestamp":1775005776705,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2005,1,20]],"date-time":"2005-01-20T00:00:00Z","timestamp":1106179200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2005,2]]},"abstract":"<jats:p>Increased release of thromboxane A<jats:sub>2<\/jats:sub> (TXA<jats:sub>2<\/jats:sub>) has been shown to be involved in inflammatory bowel diseases. In the present study, we have investigated the effect of a stable TXA<jats:sub>2<\/jats:sub> analogue (STA<jats:sub>2<\/jats:sub>) on the electrical parameters in isolated human colonic mucosa. In the human mucosa set between Ussing chambers, STA<jats:sub>2<\/jats:sub> stimulated Cl<jats:sup>\u2212<\/jats:sup> secretion in a concentration\u2010dependent manner with an EC<jats:sub>50<\/jats:sub> of 0.06 \u03bc<jats:sc>m<\/jats:sc>. The STA<jats:sub>2<\/jats:sub>\u2010induced Cl<jats:sup>\u2212<\/jats:sup> secretion was significantly inhibited by ONO\u20103708 (10 \u03bc<jats:sc>m<\/jats:sc>), a specific TXA<jats:sub>2<\/jats:sub> receptor antagonist. The effect of STA<jats:sub>2<\/jats:sub> (0.3 \u03bc<jats:sc>m<\/jats:sc>) was independent of the colonic segment from which the tissue was obtained, from caecum to rectum. Chromanol 293B, an inhibitor of the cAMP\u2010dependent KvLQT1 channel, attenuated the STA<jats:sub>2<\/jats:sub>\u2010induced Cl<jats:sup>\u2212<\/jats:sup> secretion in the human colonic mucosa (IC<jats:sub>50<\/jats:sub> value 1.18 \u03bc<jats:sc>m<\/jats:sc>). We found that KvLQT1 mRNA and protein were expressed in all the tested segments of the human colon. The STA<jats:sub>2<\/jats:sub>\u2010induced Cl<jats:sup>\u2212<\/jats:sup> secretion was significantly inhibited by 8\u2010bromo\u20102\u2032\u2010monobutyryladenosine\u20103\u2032,5\u2032\u2010cyclic monophosphorothioate (50 \u03bc<jats:sc>m<\/jats:sc>), a membrane\u2010permeant cAMP antagonist. STA<jats:sub>2<\/jats:sub> (0.3 \u03bc<jats:sc>m<\/jats:sc>) significantly increased the intracellular cAMP levels and the short\u2010circuit current via TXA<jats:sub>2<\/jats:sub> receptor in a human colonic cell line. These results suggest that the TXA<jats:sub>2<\/jats:sub>\u2010induced Cl<jats:sup>\u2212<\/jats:sup> secretion in the colon is mediated via the cAMP pathway in addition to the Ca<jats:sup>2+<\/jats:sup>\u2013calmodulin pathway which was previously reported.<\/jats:p>","DOI":"10.1113\/jphysiol.2004.077776","type":"journal-article","created":{"date-parts":[[2004,12,21]],"date-time":"2004-12-21T01:12:48Z","timestamp":1103591568000},"page":"885-897","source":"Crossref","is-referenced-by-count":9,"title":["Cyclic AMP\u2010dependent Cl<sup>\u2212<\/sup> secretion induced by thromboxane A<sub>2<\/sub> in isolated human 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