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This Article Full Text Full Text (PDF) All Versions of this Article: 551/1/207    most recent jphysiol.2003.041921v1 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 Sakai, H. Articles by Takeguchi, N. Search for Related Content PubMed PubMed Citation Articles by Sakai, H. Articles by Takeguchi, N.

Inhibition of small-conductance Cl^- channels by the interleukin-1-stimulated production of superoxide in rabbit gastric parietal cells

Hideki Sakai, Yuta Ohira, Akiko Tanaka, Tomoyuki Suzuki, Akira Ikari*, Magotoshi Morii and Noriaki Takeguchi

We have shown previously that the G protein-coupled production of superoxide anion (O₂^-) leads to closure of small-conductance Cl^- channels (0.3-0.4 pS) in the basolateral membrane of rabbit parietal cells. In the present study, effects of interleukin-1 (IL-1) on the Cl^- channel were investigated. In the whole-cell patch-clamp recording, IL-1 (0.3-10 ng ml^-1) inhibited the whole-cell Cl^- current recorded from a parietal cell within isolated rabbit gastric glands. Variance noise analysis of the whole-cell Cl^- current showed that the single channel conductance of the Cl^- channel that is sensitive to IL-1 is 0.37 pS. The IL-1 (1 ng ml^-1)-induced decrease of the Cl^- current was abolished by anti-IL-1 antibody (2 µg ml^-1), recombinant IL-1 receptor antagonist (500 ng ml^-1), GDPS (500 µM) and superoxide dismutase (100 units ml^-1), a scavenger of O₂^-. Northern blot analysis showed that the mRNA of the IL-1 receptor was selectively expressed in rabbit gastric parietal cells. In the dihydrofluorescein diacetate-loaded single parietal cells in gastric glands, IL-1 (0.3-10 ng ml^-1) stimulated the production of oxygen radicals. Y-27632 (1-10 µM), a specific Rho-kinase inhibitor, and fluvastatin (10 µM), an indirect inhibitor for Rho proteins, significantly inhibited the IL-1-induced effects on the channel activity and production of oxygen radicals. IL-1 (0.3-10 ng ml^-1) activated Rho in the parietal cells. These results indicate that IL-1 binds to the IL-1 receptor of gastric parietal cells and inhibits the small-conductance Cl^- channel via the G protein-mediated Rho/Rho-kinase-dependent production of O₂^-.

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