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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 562/3/885    most recent jphysiol.2004.077776v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Horikawa, N. Articles by Sakai, H. Search for Related Content PubMed PubMed Citation Articles by Horikawa, N. Articles by Sakai, H.

¹ Department of Surgery II, Faculty of Medicine
² Department of Pharmaceutical Physiology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan

Increased release of thromboxane A₂ (TXA₂) has been shown to be involved in inflammatory bowel diseases. In the present study, we have investigated the effect of a stable TXA₂ analogue (STA₂) on the electrical parameters in isolated human colonic mucosa. In the human mucosa set between Ussing chambers, STA₂ stimulated Cl^– secretion in a concentration-dependent manner with an EC₅₀ of 0.06 µM. The STA₂-induced Cl^– secretion was significantly inhibited by ONO-3708 (10 µM), a specific TXA₂ receptor antagonist. The effect of STA₂ (0.3 µM) was independent of the colonic segment from which the tissue was obtained, from caecum to rectum. Chromanol 293B, an inhibitor of the cAMP-dependent KvLQT1 channel, attenuated the STA₂-induced Cl^– secretion in the human colonic mucosa (IC₅₀ value 1.18 µM). We found that KvLQT1 mRNA and protein were expressed in all the tested segments of the human colon. The STA₂-induced Cl^– secretion was significantly inhibited by 8-bromo-2'-monobutyryladenosine-3',5'-cyclic monophosphorothioate (50 µM), a membrane-permeant cAMP antagonist. STA₂ (0.3 µM) significantly increased the intracellular cAMP levels and the short-circuit current via TXA₂ receptor in a human colonic cell line. These results suggest that the TXA₂-induced Cl^– secretion in the colon is mediated via the cAMP pathway in addition to the Ca²⁺–calmodulin pathway which was previously reported.

(Received 20 October 2004; accepted after revision 7 December 2004; first published online 20 December 2004)
Corresponding author H. Sakai: Department of Pharmaceutical Physiology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan. Email: sakaih{at}ms.toyama-mpu.ac.jp

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