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

Am J Physiol Cell Physiol. 2009 Apr;296(4):C654-62. doi: 10.1152/ajpcell.00509.2008. Epub 2008 Dec 3.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line
  • Cell Polarity
  • Enterocytes / drug effects
  • Enterocytes / metabolism*
  • Intestinal Absorption* / drug effects
  • Intestine, Small / cytology
  • Intestine, Small / drug effects
  • Intestine, Small / metabolism*
  • Iodides / metabolism*
  • Iodine Radioisotopes
  • Kinetics
  • Male
  • Mice
  • Microvilli / metabolism
  • Perchlorates / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Pertechnetate Tc 99m / metabolism
  • Symporters / antagonists & inhibitors
  • Symporters / metabolism*
  • Thyroid Gland / metabolism


  • Iodides
  • Iodine Radioisotopes
  • Perchlorates
  • Symporters
  • sodium-iodide symporter
  • Sodium Pertechnetate Tc 99m
  • perchlorate