胃酸分泌細胞におけるK⁺-Cl⁻ cotransporterの発現

抄録

For gastric acid (HCl) secretion, protons are actively secreted by H⁺,K⁺-ATPase in the apical membrane of gastric parietal cells, but it has not been established what molecule contributes to Cl⁻ secretion. K⁺-Cl⁻ cotransporter (KCC) plays a significant role in epithelial transport and cell volume regulation. Four KCC isoforms have been cloned. KCC1, 3, 4 are widely expressed and KCC2 is neuron specific. However, the expression of KCC isoforms in stomach has not been reported. Here we examined whether the KCC isoforms are expressed in gastric parietal cells. Western blot analysis showed that KCC3 and KCC4 were expressed in isolated gastric mucosa of rats and mice. Immunohistochemistry in the isolated gastric mucosa showed that KCC3 was expressed in the basolateral membrane and KCC4 was expressed in the apical membrane of the gastric parietal cells. Interestingly, KCC3 and KCC4 were abundantly expressed in the parietal cells located at luminal segment of the gland. Because luminal segment parietal cells are much more active in HCl secretion than those of the basal segment, KCC3 and KCC4 may be involved in the mechanism of HCl secretion. We constructed the T-REx system for KCC3 in the LLC-PK1 cells. Tetracycline-induced expression of KCC3 protein significantly increased ouabain-sensitive Na⁺,K⁺-ATPase activity. [J Physiol Sci. 2006;56 Suppl:S71]