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

Nicola JP, Basquin C, Portulano C, Reyna-Neyra A, Paroder M, Carrasco N. The Na+/I- symporter mediates active iodide uptake in the intestine. Am J Physiol Cell Physiol 296: C654-C662, 2009. First published December 3, 2008; doi:10.1152/ajpcell.00509.2008.-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.