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- Title
Cyclic AMP-dependent Cl<sup>−</sup> secretion induced by thromboxane A<sub>2</sub> in isolated human colon.
- Authors
Horikawa, Naoki; Suzuki, Tomoyuki; Uchiumi, Takaoki; Minamimura, Tetsuji; Tsukada, Kazuhiro; Takeguchi, Noriaki; Sakai, Hideki
- Abstract
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 0.06μm. The STA2-induced Cl− secretion was significantly inhibited by ONO-3708 (10μm), a specific TXA2 receptor antagonist. The effect of STA2 (0.3μm) 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 1.18μm). 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 (50μm), a membrane-permeant cAMP antagonist. STA2 (0.3μm) 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.
- Subjects
THROMBOXANES; INFLAMMATORY bowel diseases; MUCOUS membranes; COLON (Anatomy); CELL lines
- Publication
Journal of Physiology, 2005, Vol 562, Issue 3, p885
- ISSN
0022-3751
- Publication type
Article
- DOI
10.1113/jphysiol.2004.077776