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The secretin receptor is functionally expressed in the basolateral membrane of the HCO<jats:sub>3<\/jats:sub><jats:sup>\u2013<\/jats:sup>\u2010secreting \u03b2\u2010intercalated cells of the collecting duct. Here it activates a fast and efficient secretion of HCO<jats:sub>3<\/jats:sub><jats:sup>\u2013<\/jats:sup> into the urine serving to normalize metabolic alkalosis. The ability to acutely increase renal base excretion is entirely dependent on functional pendrin (SLC26A4) and CFTR, and both proteins localize to the apical membrane of the \u03b2\u2010intercalated cells. In cystic fibrosis mice and patients, this function is absent or markedly reduced. 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