Inhibition of Iodide Transport in Rat Thyroid Cells Using N-Substituted Anthranilic Acid Derivatives

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Abstract
The purpose of this study was to test the effects of chloride channel blockers on iodide uptake in thyroid cells, in the hope of eventually using these blockers to identify and isolate a putative iodide transporter. The chloride channel blockers used in this report are derivatives of N-substituted anthranilic acid and were synthesized using published procedures. For these studies FRTL-5 cells, a line of continuous-growing rat thyroid cells, were used as a model system to study effects on iodide transport. In these cells, there are at least two ways for transmembrane iodide movements, a sodium-dependent influx step and a proposed channel that normally mediates iodide efflux. Two derivatives studied decreased iodide accumulation in FRTL-5 cells, but were found also to lower intracellular pH and ATP levels. To simplify interpretation of the effect of the drugs on iodide transport, we extended the studies using plasma membrane vesicles made from pig thyroid. Iodide entry in these vesicles depended on a sodium gradient and was independent of ATP levels. Iodide transport in plasma membrane vesicles and FRTL-5 cells was measured at 30 sec when the uptake was nearly linear and therefore likely to reflect iodide entry. The uptake was measured using three concentrations of iodide and three of drug. Kinetic analysis of the data described a competitive inhibition by the drugs with a Ki of approximately 250 microM. In summary, N-substituted anthranilic acid derivatives reversibly inhibit iodide entry in FRTL-5 cells and pig plasma membrane vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)

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