Characterization of small-molecule inhibitors of the sodium iodide symporter Academic Article

journal

  • Journal of Endocrinology

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 non-thyroidal cells is currently developed. However, only little information is available concerning the molecular mechanism of NIS-mediated iodide translocation. Ten small molecules have recently been 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. © 2009 Society for Endocrinology.

publication date

  • 2009/6/24

edition

  • 200

keywords

  • Active Biological Transport
  • Genes
  • High-Throughput Screening Assays
  • Iodides
  • Membranes
  • Neoplasms
  • Oocytes
  • Thyroid Diseases
  • Thyroid Epithelial Cells
  • Water
  • Xenopus
  • sodium-iodide symporter

International Standard Serial Number (ISSN)

  • 0022-0795

number of pages

  • 9

start page

  • 357

end page

  • 365