Effect of valinomycin on thyroid iodide transport and TSH-stimulated cAMP formation.
The K+ ionophore valinomycin, in concentrations as low as 0.1 microM, induces an inhibition of thyroid-stimulating hormone (TSH)-stimulated cAMP formation in cat and pig thyroid slices and isolated, trypsin-collagenase-dispersed beef thyroid cells. Valinomycin was also shown to inhibit histamine and prostaglandin E1 stimulation of thyroid cAMP formation. The inhibitory effect of valinomycin could be partially overcome by elevated (81 mM) K+ concentrations. In the absence of valinomycin, the ability of TSH to stimulate thyroid cAMP formation was dependent on extracellular K+. Chronic removal or addition of K+ to medium bathing thyroid sections was accompanied by inhibition of TSH-stimulated cAMP formation. Maximum TSH stimulation was observed at an extracellular K+ of 2.7 mM. Valinomycin had no significant effect on thyroid ATP content but did reduce the ATP-to-ADP ratio. However, chronic removal of K+ had no effect on either ATP or the ATP-to-ADP ratio. Varying extracellular Na+ from 26 to 144 mM or addition of tetrodotoxin did not affect TSH action. Valinomycin addition to thyroid slices was associated with a reduction in iodide transport as measured by the ratio of tissue to extracellular iodide concentrations. The effect of valinomycin on iodide transport was accompanied by an increase in iodide efflux that was not greater than that observed with perchlorate ion, suggesting a reduced recirculation of released iodide in valinomycin-treated tissue. These findings suggest that alterations in thyroid cell K+ permeability or intracellular K+ concentration may be accompanied by changes in TSH-induced stimulation of thyroid cAMP formation.
D000227:Adenine Nucleotides / Q000378:metabolism; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002415:Cats; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D005110:Extracellular Space / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D007454:Iodides / Q000378:metabolism*; D009994:Osmolar Concentration; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013268:Stimulation, Chemical; D013552:Swine; D013779:Tetrodotoxin / Q000494:pharmacology; D013961:Thyroid Gland / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology*; D014634:Valinomycin / Q000494:pharmacology*
D000227:Adenine Nucleotides; D007454:Iodides; D014634:Valinomycin; D013779:Tetrodotoxin; D006632:Histamine; D013972:Thyrotropin; D012964:Sodium; D000242:Cyclic AMP; D000527:Alprostadil; D011188:Potassium