In vitro investigations of the direct effects of complex anions on thyroidal iodide uptake: Identification of novel inhibitors

• Published in: Toxicology in vitro Vol. 10; no. 2; pp. 149 - 160
• Main Authors: Jones, P.A., Pendlington, R.U., Earl, L.K., Sharma, R.K., Barratt, M.D.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-04-1996; Elsevier Science
• Subjects: Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; Medical sciences; Metals and various inorganic compounds; Toxicology; IO = iodide organification; PTU = propylthiouracil; TCA = trichloroacetic acid; HICS = heat-inactivated newborn calf serum; IU = iodide uptake; MET = methimazole; TSH = thyroid stimulating hormone; HBSS = Hanks' balanced salt solution; Endocrinopathy; Permanganates; Periodates; Hexafluoantimonates; Toxicity; Hexafluophosphates; Nitrates; Thyroid gland; Perchlorates; In vitro; Tetrafluoborates; Pig; Vertebrata; Mammalia; Inorganic anion; Animal; Hexafluoarsenates; Bromides; Thiocyanates; Thyroid hormone; Artiodactyla; Mechanism of action; Ungulata
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/0887-2333(95)00114-X

Iodide uptake (IU) by thyrocytes from the plasma against chemical and electrical gradients is by a specific iodide transporter or ‘pump’. Perchlorate (ClO
4
−) and other univalent, symmetrical anions are competitive inhibitors of iodide uptake (IU), and apparent
K
i
for individual anions can be correlated with ion size. This study uses cultured thyrocytes and a broad range of anion size, in particular a series of spherical hexafluoride ions, in order to understand more about the parameters governing the activity of competitive inhibitors of IU.
125I uptake and organification by cultured porcine thyrocytes was combined with biochemical enzyme inhibition studies on thyroid peroxidase in order to identify specific effects on IU. Known inhibitors were used in a validation phase and demonstrated that a combination of the
in vitro thyrocyte
125I assay and thyroid peroxidase inhibition assay could be used to identify selective inhibitors that can be difficult to identify using thyrocytes alone. Anions of less than, or similar, volume to I
− (35.0 Å
3) were weak inhibitors with potency increasing proportional to ion size up to an apparent maximum for AsF
6
− (94.45 Å
3); this correlation was strong (
r = 0.96). PF
6
−, AsF
6
− and SbF
6
− were identified as novel inhibitors of IU, showing that the size range of anions active in IU inhibition is greater than that previously identified. The biological significance
in vivo of the inhibitory action of the hexafluoride ions is not known. Their potency in this study suggests that these anions may have the potential to affect thyroid function
in vivo if they were available systemically.