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 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 approximately 4 to approximately 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.

Collecting Duct Intercalated Cell Function and Regulation

“…The regulation of pendrin also involves glycosylation-dependent processes (104,105). In addition to the regulation of acid-base status, it appears that pendrin expressed in kidney intercalated cells plays a role in controlling iodide homeostasis as well, especially during high water intake (106). Type B intercalated cells have recently come to prominence with the discovery that the Na 1 -driven chloride/ bicarbonate exchanger (NDCBE) (107) and pendrin colocalize at the apical membrane of these cells ( Figure 6).…”

ENaC inhibition stimulates Cl−secretion in the mouse cortical collecting duct through an NKCC1-dependent mechanism

“…Kidneys were preserved by in vivo perfusion fixation and embedded in paraffin as previously described (20). We used an NKCC1 antibody (␣-wNT) raised in rabbits against a 6xHis fusion protein corresponding to amino acids 3-202 of the rat NKCC1 sequence (5), which was a generous gift from Dr. R. James Turner.…”

Angiotensin II acts through the angiotensin 1a receptor to upregulate pendrin

“…Immunoblots were performed using a rabbit anti-rat pendrin antibody (20), a generous gift of Dr. Peter Aronson, which recognizes the terminal 29 amino acids of the rat pendrin sequence and specifically detects mouse pendrin protein by immunoblotting (19).…”

“…Kidneys were preserved by in vivo perfusion fixation and embedded in paraffin as described previously (19). Pendrin immunoreactivity was detected using immunoperoxidase procedures; blocking was done with 3% H 2O2 in methanol for 30 min, followed by protein blocking using 1% Fig.…”