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.

Na + coordination at the Na2 site of the Na + /I − symporter

“…Accumulated 125 I − was released with ice-cold ethanol and then quantified in a Cobra II Gamma Counter (Packard Bioscience). DNA was determined by the diphenylamine method after trichloroacetic acid precipitation (10). Iodide uptake was expressed as picomoles of I − per microgramg DNA.…”

“…Other anions, such as perrhenate (ReO 4 − ) (5) and the environmental pollutant perchlorate (ClO 4 − ) (6), are also transported by NIS, but, surprisingly, with an electroneutral (1 Na + : 1 anion) stoichiometry. Besides the thyroid, NIS mediates active I − transport in several other tissues, including the lactating breast (7), salivary glands (7,8), stomach (9), and small intestine (10,11). The function of NIS appears to be an evolutionary adaptation to the scant amount of I − in the environment (12,13).…”

The iodide transport defect-causing mutation R124H: a δ-amino group at position 124 is critical for maturation and trafficking of the Na+/I− symporter (NIS)

“…The Na + /I 2 symporter (NIS) is a plasma membrane glycoprotein that mediates the active transport of I 2 into the thyroid gland and other tissues, such as salivary glands, gastric mucosa, small intestine and lactating breast (Altorjay et al, 2007;Nicola et al, 2009;Nicola et al, 2012;Tazebay et al, 2000;Wapnir et al, 2003). In the thyroid, I…”

Iodine Deficieency and Its Proliferation in Cancer Increase

“…Ultimately, excretion is via the kidneys with minor amounts excreted in feces. To enter DOI: 10.21859/ajlsr-0402085 cells, iodide (I -) must be co-transported with 2 molecules of sodium to overcome the electrochemical gradient [4]. This sodium/iodide symporter (NIS) is well characterized on the basement membrane of thyroid follicular cells, where it allows for requisite iodide uptake.…”