The protein kinase C pathway inhibits iodide uptake by calf thyroid cells via sodium potassium-adenosine triphosphatase

The effect of the phorbol esther phorbol myristate acetate (PMA) on iodide uptake was studied in primary cultures of calf thyroid cells. PMA caused a dose- and time-dependent inhibition of thyrotropin (TSH), forskolin, and db -cAMP stimulation, indicating an effect distal to both TSH receptor and cAM P generation. No action was found on iodide efflux, indicating a selective inhibition of iodide uptake. This inhibition was observed even after 5 minu tes of incubation, thus excluding a possible genomic action. Bisindolmaleim ide (BS), a specific inhibitor of the protein kinase C (PKC) pathway, rever ted the effect of PMA. A similar degree of inhibition of the Na+/K+ adenosi ne triphosphatase (ATPase) and iodide uptake by PMA was found, thus suggest ing a link between both parameters. These results indicate that the PKC pat hway inhibits thyroid iodide uptake by an action distal to cAMP generation and probably because of a decrease in Na+/K+-ATPase activity.