Role of pendrin in iodide balance: going with the flow

Abstract

Pendrin is expressed in the apical regions of type B and non-A, non-B intercalated cells, where it mediates Cl − absorption and HCO 3 − secretion through apical Cl − /HCO 3 − 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 H 2 O intake enhanced differences between wild-type and pendrin null mice in I − balance, suggesting that H 2 O intake modulates pendrin abundance. Raising water intake from ∼4 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 H 2 O intake modulates pendrin through the action of AVP. We observed that H 2 O intake modulated pendrin abundance even when circulating vasopressin levels were clamped. We conclude that H 2 O 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.