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Am J Physiol Cell Physiol 296: C654-C662, 2009. First published December 3, 2008; doi:10.1152/ajpcell.00509.2008
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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

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

Juan Pablo Nicola,1 Cécile Basquin,1,* Carla Portulano,1,* Andrea Reyna-Neyra,2 Monika Paroder,1 and Nancy Carrasco1

Departments of 1Molecular Pharmacology and 2Neuroscience, Albert Einstein College of Medicine, Bronx, New York

Submitted 8 October 2008 ; accepted in final form 1 December 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.

dietary iodide absorption; active iodide transport; sodium/iodide symporter; enterocyte brush border



Address for reprint requests and other correspondence: N. Carrasco, Dept. of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461 (e-mail: carrasco{at}aecom.yu.edu)







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