Differential modulation by Ca2+ of iodide transport processes in a cultured rat thyroid cell strain

Abstract

ABSTRACT The interrelationship between the roles of Ca2+ and cyclic AMP (cAMP) in the control of intracellular iodide accumulation was investigated in the continuous rat thyroid cell strain FRTL-5. Using incubation conditions designed to allow independent study of iodide uptake and efflux into the incubation medium, dibutyryl cAMP (dbcAMP) mimicked the effect of TSH in enhancing iodide uptake, but the responses to both stimulators were decreased in the presence of the Ca2+ ionophore A23187, although the ionophore was ineffective when addition was delayed until after withdrawal of the stimulators. l-Adrenaline, an α-adrenergic agonist inactive with respect to cAMP accumulation in this cell strain, was also inactive with regard to iodide uptake. The rapid efflux of iodide from FRTL-5 cells seen in response to TSH was not mimicked by dbcAMP, but was reproduced by A23187, providing evidence for the involvement of Ca2+ in the release process. Under the latter conditions, no additional effect of TSH was obtained. l-Adrenaline also stimulated iodide efflux, in support of a possible role of α-adrenergic agonists in controlling the apical membrane presentation of iodide in vivo. The observed differential effects of dbcAMP and α-adrenergic agonists on iodide uptake and efflux respectively, provide further evidence for the existence of two functionally distinct mechanisms controlling the available level of intracellular iodide. Opposing effects of free intracellular Ca2+ may, however, serve to control the activities of both influx and efflux processes since, whilst experimental increments in Ca2+ appear to promote iodide efflux through a non-cAMP-mediated pathway, inhibition by intracellular Ca2+ of thyroid cell cAMP accumulation may explain both the decreased response of iodide uptake observed in the presence of A23187, and the reduced stimulation effected by TSH under such conditions. J. Endocr. (1987) 112, 51–56