The Renal Physiology of Pendrin-Positive Intercalated Cells

• Published in: Physiological reviews 2020-07, Vol.100 (3), p.1119-1147
• Main Authors: Wall, Susan M, Verlander, Jill W, Romero, Cesar A
• Format: Article
• Language: English
• Subjects: Acid-Base Equilibrium - drug effects; Acid-Base Equilibrium - physiology; Aldosterone - pharmacology; Angiotensin II - pharmacology; Animals; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Humans; Kidney - cytology; Kidney - physiology; Review; Sulfate Transporters - metabolism
• ISSN: 0031-9333; 1522-1210
• DOI: 10.1152/physrev.00011.2019

Intercalated cells (ICs) are found in the connecting tubule and the collecting duct. Of the three IC subtypes identified, type B intercalated cells are one of the best characterized and known to mediate Cl absorption and HCO secretion, largely through the anion exchanger pendrin. This exchanger is thought to act in tandem with the Na -dependent Cl /HCO exchanger, NDCBE, to mediate net NaCl absorption. Pendrin is stimulated by angiotensin II and aldosterone administration via the angiotensin type 1a and the mineralocorticoid receptors, respectively. It is also stimulated in models of metabolic alkalosis, such as with NaHCO administration. In some rodent models, pendrin-mediated HCO secretion modulates acid-base balance. However, of probably more physiological or clinical significance is the role of these pendrin-positive ICs in blood pressure regulation, which occurs, at least in part, through pendrin-mediated renal Cl absorption, as well as their effect on the epithelial Na channel, ENaC. Aldosterone stimulates ENaC directly through principal cell mineralocorticoid hormone receptor (ligand) binding and also indirectly through its effect on pendrin expression and function. In so doing, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. In addition to its role in Na and Cl balance, pendrin affects the balance of other ions, such as K and I . This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contribution of pendrin-positive ICs in the kidney to distal nephron function and blood pressure.