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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0246v1 200/3/357    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lindenthal, S. Articles by Pourcher, T. Search for Related Content PubMed PubMed Citation Articles by Lindenthal, S. Articles by Pourcher, T.

S Lindenthal, TIRO, UNSA, Nice, France
N Lecat-Guillet, iBiTecS, CEA, Gif-sur-Yvette, France
A Ondo-Mendez, TIRO, UNSA, Nice, France
Y Ambroise, iBiTecS, CEA, Gif-sur-Yvette, France
B Rousseau, iBiTecS, CEA, Gif-sur-Yvette, France
T Pourcher, TIRO CEA, University of Nice, Nice, 06107, France

Correspondence: Thierry Pourcher, Email: pourcher{at}unice.fr

Abstract

The sodium/iodide symporter (NIS) mediates the active transport of iodide from the bloodstream into thyrocytes. NIS function is strategic for the diagnosis and treatment of various thyroid diseases. In addition, a promising anti-cancer strategy based on targeted NIS gene transfer in nonthyroidal cells is currently developed. However, only little information is available concerning the molecular mechanism of NIS-mediated iodide translocation. Ten small-molecules were recently identified using a high-throughput screening method for their inhibitory effect on iodide uptake of NIS-expressing mammalian cells. In the present study, we analyzed these compounds for their rapid and reversible effects on the iodide-induced current in NIS-expressing Xenopus oocytes. Four molecules almost completely inhibited the iodide-induced current; for three of them the effect was irreversible, for one compound the initial current could be fully re-established after washout. Three molecules showed a rapid inhibitory effect of about 75%, half of which was reversible. Another three compounds inhibited the iodide-induced current from 10% to 50%. Some molecules altered the membrane conductance by themselves, i.e. in the absence of iodide. For one of these molecules the observed effect was also found in water-injected oocytes whereas for some others the iodide-independent effect was associated with NIS expression. The tested molecules show a surprisingly high variability in their possible mode of action, and thus are promising tools for further functional characterization of NIS on a molecular level, and they could be useful for medical applications.