IN-VITRO INVESTIGATIONS OF THE DIRECT EFFECTS OF COMPLEX ANIONS ON THYROIDAL IODIDE UPTAKE - IDENTIFICATION OF NOVEL INHIBITORS

Iodide uptake (IU) by thyrocytes from the plasma against chemical and electrical gradients is by a specific iodide transporter or 'pump'. Pe rchlorate (ClO4-) and other univalent, symmetrical anions are competit ive inhibitors of iodide uptake (IU), and apparent K-i for individual anions can be correlated with ion size. This study uses cultured thyro cytes and a broad range of anion size, in particular a series of spher ical hexafluoride ions, in order to understand more about the paramete rs governing the activity of competitive inhibitors of IU. I-125 uptak e and organification by cultured porcine thyrocytes was combined with biochemical enzyme inhibition studies on thyroid peroxidase in order t o identify specific effects on IU. Known inhibitors were used in a val idation phase and demonstrated that a combination of the in vitro thyr ocyte I-125 assay and thyroid peroxidase inhibition assay could be use d to identify selective inhibitors that can be difficult to identify u sing thyrocytes alone. Anions of less than, or similar, volume to I- ( 35.0 Angstrom(3)) were weak inhibitors with potency increasing proport ional to ion size up to an apparent maximum for AsF6- (94.45 Angstrom( 3)); this correlation was strong (r = 0.96). PF6-, AsF6- and SbF6- wer e identified as novel inhibitors of IU, showing that the size range of anions active in IU inhibition is greater than that previously identi fied. The biological significance in vivo of the inhibitory action of the hexafluoride ions is not known. Their potency in this study sugges ts that these anions may have the potential to affect thyroid function in vivo if they were available systemically. Copyright (C) 1996 Elsev ier Science Ltd.