Phorbol myristate acetate inhibits alpha 1-adrenergically but not thyrotropin-regulated functions in FRTL-5 rat thyroid cells.
The iodination of thyroglobulin and the formation of thyroid hormones are regulated by alpha 1-adrenergic agents as well as TSH in rat FRTL-5 cells. The regulatory effects of the alpha-1-adrenergic agents and TSH on both of these processes are associated with an increase in cytosolic Ca2+ and an increase in that component of iodide efflux that is representative of the movement of iodide from the thyroid cell into the follicular lumen. When FRTL-5 cells are preincubated with phorbol myristate acetate (PMA) for at least 3 min, the norepinephrine-stimulated changes in cytosolic Ca2+ levels and iodide efflux are inhibited. In contrast, PMA pretreatment has no effect on iodide efflux and actually enhances the changes in cytosolic Ca2+ induced by TSH. Phorbol myristate acetate pretreatment has no effect on TSH-stimulated cAMP-mediated iodide uptake in FRTL-5 cells, nor does it affect the binding parameters of the alpha 1-adrenergic receptor antagonist prazosin. These data suggest that protein kinase C is involved in a feedback mechanism regulating alpha 1-adrenergic but not TSH-induced changes associated with the iodination of thyroglobulin and the formation of thyroid hormones; and that this feedback effect occurs after the step of ligand binding but before the increase in cytosolic Ca2+ induced by the alpha 1-adrenergic agents.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D007454:Iodides / Q000378:metabolism; D007700:Kinetics; D009638:Norepinephrine / Q000494:pharmacology*; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology*
D007454:Iodides; D011942:Receptors, Adrenergic, alpha; D013972:Thyrotropin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin