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Thanks for your support. We appreciate your feedback. It is invaluable to us! Chloride (Cl−) transport plays important roles in numerous physiological processes, ranging from acid-base regulation and volume homeostasis, to the extrusion of anions and the release of hormones such as aldosterone, insulin and glucagon. Consequently, alterations in Cl− transport have been associated with several diseases, including hypertension, asthma, emphysema and cystic fibrosis, to mention just a few. Potassium (K+) secretion is primarily controlled by the epithelial Na+ channel (ENaC) in the apical membrane of aldosterone-sensitive distal nephron (ASDN) cells. Aldosterone binding to the mineralocorticoid receptor (MR) activates the transcription of the β and γ subunit of ENaC (reviewed in Cummins, F. J. et al., Nature, 2000, 408:1047-1051). Na+/H+ exchange proteins have been shown to be important for maintaining the resting membrane potential and regulating cell volume (reviewed in Kawano, T., J. Clin. Invest., 1993, 91:1212-1222). NHE3 is an apical membrane protein that is uniquely regulated by intracellular pH (pHcyt), such that an acidic pH stimulates, while a basic pH inhibits, NHE3-mediated transport. This regulation seems to be mediated by the NHE3 cytoplasmic regulatory domain, since it is possible to isolate a region of the NHE3 C-terminal tail (amino acids 1251-1286 of isoform 3) that is necessary and sufficient for this regulation (Ren, Y. et al., J. Biol. Chem., 2000, 275:23497-23502). NHE8, also known as solute carrier family 9 (sodium/phosphate co-transporter) member 3 (Slc9a3), was recently identified as a gene encoding an intestinal Na+/Pi cotransporter. NHE8 is present in all segments of the small intestine and the colon. Northern analysis of tissues from the rat identified NHE8 in the kidney and liver as well as small intestine, suggesting that it may be responsible for net Pi absorption (Nelson, P. F. et al., Proc. Natl. Acad. Sci. USA, 2002, 99:7261-7266).; the site




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