The Na+/I−symporter mediates active iodide uptake in the intestine

Abstract

Absorption of dietary iodide, presumably in the small intestine, is the first step in iodide (I−) utilization. From the bloodstream, I−is actively taken up via the Na+/I−symporter (NIS) in the thyroid for thyroid hormone biosynthesis and in such other tissues as lactating breast, which supplies I−to the newborn in the milk. The molecular basis for intestinal I−absorption is unknown. We sought to determine whether I−is actively accumulated by enterocytes and, if so, whether this process is mediated by NIS and regulated by I−itself. NIS expression was localized exclusively at the apical surface of rat and mouse enterocytes. In vivo intestine-to-blood transport of pertechnetate, a NIS substrate, was sensitive to the NIS inhibitor perchlorate. Brush border membrane vesicles accumulated I−in a sodium-dependent, perchlorate-sensitive manner with kinetic parameters similar to those of thyroid cells. NIS was expressed in intestinal epithelial cell line 6, and I−uptake in these cells was also kinetically similar to that in thyrocytes. I−downregulated NIS protein expression and its own NIS-mediated transport both in vitro and in vivo. We conclude that NIS is functionally expressed on the apical surface of enterocytes, where it mediates active I−accumulation. Therefore, NIS is a significant and possibly central component of the I−absorption system in the small intestine, a system of key importance for thyroid hormone biosynthesis and thus systemic intermediary metabolism.