A 96-well automated radioiodide uptake assay for sodium/iodide symporter inhibitors.

A high-throughput screening method based on radioiodide uptake in human embryonic kidney 293 cells expressing the human sodium/iodide symporter was developed. Central to assay development was a homogeneous cell culture in the 96-well microplate coupled with the use of scintillation proximity technology. The assay is fast and highly reproducible with a Z' greater than 0.8. The automated procedure allows the screening of 4,000 compounds per day. Using this methodology, several known substrates of the sodium/iodide symporter were evaluated in a single day. Inhibition of iodide uptake was shown to follow the series PF(6)(-) > ClO(4)(-) > BF(4)(-) > SCN(-) >> NO(3)(-) > IO(4)(-) > N(3)(-) >> Br(-), in accord with the literature. This method represents an initial approach to the search for inhibitors of iodide transport mediated by the sodium/iodide symporter.

[1]  J. Darcourt,et al.  From the molecular characterization of iodide transporters to the prevention of radioactive iodide exposure. , 2006, Biochimie.

[2]  B. Rousset,et al.  Three-dimensional organization of thyroid cells into follicle structures is a pivotal factor in the control of sodium/iodide symporter expression. , 2006, Endocrinology.

[3]  E. Dadachova,et al.  Kinetics of Perrhenate Uptake and Comparative Biodistribution of Perrhenate, Pertechnetate, and Iodide by Nai Symporter–expressing Tissues in Vivo , 2022 .

[4]  B. Rousset,et al.  The porcine sodium/iodide symporter gene exhibits an uncommon expression pattern related to the use of alternative splice sites not present in the human or murine species. , 2003, Endocrinology.

[5]  C. Ginter,et al.  The sodium/iodide Symporter (NIS): characterization, regulation, and medical significance. , 2003, Endocrine reviews.

[6]  T. Pourcher,et al.  Cloning of the mouse sodium iodide symporter and its expression in the mammary gland and other tissues. , 2001, The Journal of endocrinology.

[7]  A. De la Vieja,et al.  Molecular analysis of the sodium/iodide symporter: impact on thyroid and extrathyroid pathophysiology. , 2000, Physiological reviews.

[8]  Thomas D. Y. Chung,et al.  A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays , 1999, Journal of biomolecular screening.

[9]  J. Braekman,et al.  The Na+-I– cotransporter of the thyroid: characterisation of new inhibitors , 1997, Pflügers Archiv.

[10]  Qing-Rong Liu,et al.  Cloning of the human sodium lodide symporter. , 1996, Biochemical and biophysical research communications.

[11]  R. Sharma,et al.  In vitro investigations of the direct effects of complex anions on thyroidal iodide uptake: Identification of novel inhibitors. , 1996, Toxicology in vitro : an international journal published in association with BIBRA.

[12]  N. Carrasco,et al.  Cloning and characterization of the thyroid iodide transporter , 1996, Nature.

[13]  S. P. Porterfield,et al.  The role of thyroid hormones in prenatal and neonatal neurological development--current perspectives. , 1993, Endocrine reviews.

[14]  J. Dumont,et al.  Anion selectivity by the sodium iodide symporter. , 2003, Endocrinology.

[15]  J. Wolff.  TRANSPORT OF IODIDE AND OTHER ANIONS IN THE THYROID GLAND. , 1964, Physiological reviews.