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The molecular mechanism of CFTR‐ and secretin‐dependent renal bicarbonate excretion
Author(s) -
Berg Peder,
Svendsen Samuel L.,
Sorensen Mads Vaarby,
Schreiber Rainer,
Kunzelmann Karl,
Leipziger Jens
Publication year - 2021
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp281285
Subject(s) - endocrinology , medicine , pendrin , excretion , chemistry , secretin , bicarbonate , cystic fibrosis transmembrane conductance regulator , reabsorption , apical membrane , cystic fibrosis , secretion , renal physiology , kidney , biology , biochemistry , membrane , transporter , gene
Abstract This review summarizes the newly discovered molecular mechanism of secretin‐stimulated urine HCO 3 – excretion and the role of cystic fibrosis transmembrane conductance regulator (CFTR) in renal HCO 3 – excretion. The secretin receptor is functionally expressed in the basolateral membrane of the HCO 3 – ‐secreting β‐intercalated cells of the collecting duct. Here it activates a fast and efficient secretion of HCO 3 – 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 β‐intercalated cells. In cystic fibrosis mice and patients, this function is absent or markedly reduced. We discuss that the alkaline tide, namely the transient urine alkalinity after a meal, has now received a clear physiological explanation.