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 cAMP generation. No action was found on iodide efflux, indicating a selective inhibition of iodide uptake. This inhibition was observed even after 5 minutes of incubation, thus excluding a possible genomic action. Bisindolmaleimide (BS), a specific inhibitor of the protein kinase C (PKC) pathway, reverted the effect of PMA. A similar degree of inhibition of the Na+/K+ adenosine triphosphatase (ATPase) and iodide uptake by PMA was found, thus suggesting a link between both parameters. These results indicate that the PKC pathway inhibits thyroid iodide uptake by an action distal to cAMP generation and probably because of a decrease in Na+/K+-ATPase activity.
Bocanera
L V
LV
Division Bioquímica Nuclear, Unidad de Actividad Radiobiología, Comisión Nacional de Energía Atómica, Buenos Aires, Argentina. bocanera@cnea.gov.ar
Krawiec
L
L
Nocetti
G
G
Juvenal
G J
GJ
Silberschmidt
D
D
Pisarev
M A
MA
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007454:Iodides / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics*; D007455:Iodine / Q000493:pharmacokinetics; D008301:Maleimides / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology; D013997:Time Factors
D004791:Enzyme Inhibitors; D007211:Indoles; D007454:Iodides; D008301:Maleimides; D005576:Colforsin; D003994:Bucladesine; D013972:Thyrotropin; D007455:Iodine; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase; C088060:bisindolylmaleimide; D013755:Tetradecanoylphorbol Acetate