Inhibition of small‐conductance Cl− channels by the interleukin‐1β‐stimulated production of superoxide in rabbit gastric parietal cells
Inhibition of small‐conductance Cl− channels by the interleukin‐1β‐stimulated production of superoxide in rabbit gastric parietal cells
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DOI：
10.1111/j.1469-7793.2003.00207.x
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发表时间：
2003-08
期刊：
影响因子：
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通讯作者：
H. Sakai;Y. Ohira;A. Tanaka;Tomoyuki Suzuki;A. Ikari;M. Morii;N. Takeguchi
中科院分区：
文献类型：
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作者：
H. Sakai;Y. Ohira;A. Tanaka;Tomoyuki Suzuki;A. Ikari;M. Morii;N. 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‐1β (IL‐1β) on the Cl− channel were investigated. In the whole‐cell patch‐clamp recording, IL‐1β (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‐1β is 0.37 pS. The IL‐1β (1 ng ml−1)‐induced decrease of the Cl− current was abolished by anti‐IL‐1β antibody (2 μg ml−1), recombinant IL‐1 receptor antagonist (500 ng ml−1), GDPβS (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‐1β (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‐1β‐induced effects on the channel activity and production of oxygen radicals. IL‐1β (0.3–10 ng ml−1) activated Rho in the parietal cells. These results indicate that IL‐1β 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−.
