Role of pendrin in iodide balance: going with the flow

Kim YH, Pham TD, Zheng W, Hong S, Baylis C, Pech V, Beierwaltes WH, Farley DB, Braverman LE, Verlander JW, Wall SM. Role of pendrin in iodide balance: going with the flow. Am J Physiol Renal Physiol 297: F1069-F1079, 2009. First published July 15, 2009; doi:10.1152/ajprenal.90581.2008.-Pendrin is expressed in the apical regions of type B and non-A, non-B intercalated cells, where it mediates Cl- absorption and HCO3- secretion through apical Cl-/HCO3- exchange. Since pendrin is a robust I- transporter, we asked whether pendrin is upregulated with dietary I- restriction and whether it modulates I- balance. Thus I- balance was determined in pendrin null and in wild-type mice. Pendrin abundance was evaluated with immunoblots, immunohistochemistry, and immunogold cytochemistry with morphometric analysis. While pendrin abundance was unchanged when dietary I- intake was varied over the physiological range, I- balance differed in pendrin null and in wild-type mice. Serum I- was lower, while I- excretion was higher in pendrin null relative to wild-type mice, consistent with a role of pendrin in renal I- absorption. Increased H2O intake enhanced differences between wild-type and pendrin null mice in I- balance, suggesting that H2O intake modulates pendrin abundance. Raising water intake from similar to 4 to similar to 11 ml/day increased the ratio of B cell apical plasma membrane to cytoplasm pendrin label by 75%, although circulating renin, aldosterone, and serum osmolality were unchanged. Further studies asked whether H2O intake modulates pendrin through the action of AVP. We observed that H2O intake modulated pendrin abundance even when circulating vasopressin levels were clamped. We conclude that H2O intake modulates pendrin abundance, although not likely through a direct, type 2 vasopressin receptor-dependent mechanism. As water intake rises, pendrin becomes increasingly critical in the maintenance of Cl- and I- balance.