Association of the changes in cytosolic Ca2+ and iodide efflux induced by thyrotropin and by the stimulation of α1-adrenergic receptors in cultured rat thyroid cells

Thyrotropin causes a time- and concentration-dependent increase in cytosolic Ca²⁺ in FRTL-5 rat thyroid cells as measured by Quin 2 fluorescence; the half-maximal response occurs in response to 1 x 10^-7 M thyrotropin. The effect of added thyrotropin is the same whether cells have been previously and chronically exposed to thyrotropin or whether they have been thyrotropin 'starved' for several days. The thyrotropin effect on cytosolic Ca²⁺ has no relationship to intracellular cAMP levels with respect to dose and time course. Norepinehrine (1 x 10^-7 M) also causes increases in cytosolic Ca²⁺ in FRTL-5 thyroid cells. With the use of a variety of adrenergic inhibitors, norepinephrine was found to exert its effect via an α₁-adrenergic receptor. The exposure of FRTL-5 cells to physiological thyrotropin concentrations enhances the effect on cytosolic Ca²⁺ level induced by norepinephrine in vitro; the shape of the dose-response curve indicates a cooperative effect of the thyrotropin and norepinephrine. The increase in cytosolic Ca²⁺ seems to be derived from an intracellular pool rather than from the extracellular space. It is not prevented by nifedipine, a blocker of Ca²⁺ channel; it is present in cells exposed to ethylene glycol bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid; and it is not associated with increased Ca²⁺ uptake into the cell. The thyrotropin- and norepinephrine-induced increase in cytosolic Ca²⁺ parallels the efflux of iodide and the organification of thyroglobulin in a dose-dependent manner.