title: Relative potencies and additivity of perchlorate, thiocyanate, nitrate, and iodide on the inhibition of radioactive iodide uptake by the human sodium iodide symporter.
abstract: The presence of perchlorate (ClO(4) (-)) in some U.S. drinking water supplies has raised concern about potential adverse thyroidal health effects, because ClO(4) (-) is known to competitively inhibit iodide uptake at the sodium iodide symporter (NIS). Humans are nutritionally and environmentally exposed to other competitive inhibitors of iodide uptake, including thiocyanate (SCN(-)) and nitrate (NO(3) (-)). The joint inhibiting effects of these three anions was studied by exposing Chinese hamster ovary cells stably expressing human NIS to varying concentrations of each anion separately, and in combination, and conducting measurements of (125)I(-) uptake. The entire data set was fit to a single Hill equation using maximum likelihood. The relative potency of ClO(4) (-) to inhibit (125)I(-) uptake at the NIS was found to be 15, 30 and 240 times that of SCN(-), I(-), and NO(3) (-) respectively on a molar concentration basis, with no evidence of synergism. These results are consistent with a common mode of action by these anions of simple competitive interaction, in which a concentration of any one of ClO(4) (-) SCN(-), and NO(3) (-), occurring either individually or as part of a mixture of the three anions, is indistinguishable from a concentration or dilution of either one of the remaining two ions in inhibiting iodine uptake at the NIS.
authors.affiliation: Department of Endocrinology and Metabolism and Research Center of Excellence for the Study of Damages to the Nervous and Endocrine Systems produced by Environmental, Alimentary and Pharmacological Agents, University of Pisa, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Tonacchera
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinchera
authors.forename: Antonio
authors.initials: A
authors.lastname: Dimida
authors.forename: Eleonora
authors.initials: E
authors.lastname: Ferrarini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Agretti
authors.forename: Paolo
authors.initials: P
authors.lastname: Vitti
authors.forename: Ferruccio
authors.initials: F
authors.lastname: Santini
authors.forename: Kenny
authors.initials: K
authors.lastname: Crump
authors.forename: John
authors.initials: J
authors.lastname: Gibbs
mesh_terms: D000465:Algorithms; D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D007454:Iodides / Q000378:metabolism* / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008954:Models, Biological; D009566:Nitrates / Q000494:pharmacology*; D010472:Perchlorates / Q000494:pharmacology*; D027981:Symporters / Q000378:metabolism*; D013861:Thiocyanates / Q000494:pharmacology*; D014162:Transfection; D000099209:Sodium-Iodide Symporters
chemical_list: D001323:Autoantibodies; D007454:Iodides; D007457:Iodine Radioisotopes; D009566:Nitrates; D010472:Perchlorates; D027981:Symporters; D013861:Thiocyanates; D000099209:Sodium-Iodide Symporters