Regulation of Blood Pressure and Salt Balance By Pendrin-Positive Intercalated Cells: Donald Seldin Lecture 2020

Intercalated cells make up about a third of all cells within the connecting tubule and the collecting duct and are subclassified as type A, type B and non-A, non-B based on the subcellular distribution of the H + -ATPase, which dictates whether it secretes H + or HCO 3 − . Type B intercalated cells mediate Cl − absorption and HCO 3 − secretion, which occurs largely through the anion exchanger pendrin. Pendrin is stimulated by angiotensin II via the angiotensin type 1a receptor and by aldosterone through MR (mineralocorticoid receptor). Aldosterone stimulates pendrin expression and function, in part, through the alkalosis it generates. Pendrin-mediated HCO 3 − secretion increases in models of metabolic alkalosis, which attenuates the alkalosis. However, pendrin-positive intercalated cells also regulate blood pressure, at least partly, through pendrin-mediated Cl − absorption and through their indirect effect on the epithelial Na + channel, ENaC. This aldosterone-induced increase in pendrin secondarily stimulates ENaC, thereby contributing to the aldosterone pressor response. This review describes the contribution of pendrin-positive intercalated cells to Na + , K + , Cl − and acid-base balance.