The Na+/I- symporter mediates active iodide uptake in the intestine.
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.
Nicola
Juan Pablo
JP
Dept. of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA.
Basquin
Cécile
C
Portulano
Carla
C
Reyna-Neyra
Andrea
A
Paroder
Monika
M
Carrasco
Nancy
N
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
D007454:Iodides; D007457:Iodine Radioisotopes; D010472:Perchlorates; D013670:Sodium Pertechnetate Tc 99m; D027981:Symporters; D000099209:Sodium-Iodide Symporters; C494474:perchlorate