title: 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.
authors.affiliation: Dept. of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Nicola
authors.forename: Cécile
authors.initials: C
authors.lastname: Basquin
authors.forename: Carla
authors.initials: C
authors.lastname: Portulano
authors.forename: Andrea
authors.initials: A
authors.lastname: Reyna-Neyra
authors.forename: Monika
authors.initials: M
authors.lastname: Paroder
authors.forename: Nancy
authors.initials: N
authors.lastname: Carrasco
mesh_terms: D000818:Animals; D002460:Cell Line; D016764:Cell Polarity; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007454:Iodides / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D051379:Mice; D008871:Microvilli / Q000378:metabolism; D010472:Perchlorates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013670:Sodium Pertechnetate Tc 99m / Q000378:metabolism; D027981:Symporters / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013961:Thyroid Gland / Q000378:metabolism; D000099209:Sodium-Iodide Symporters
chemical_list: D007454:Iodides; D007457:Iodine Radioisotopes; D010472:Perchlorates; D013670:Sodium Pertechnetate Tc 99m; D027981:Symporters; D000099209:Sodium-Iodide Symporters; C494474:perchlorate