Inhibition of intermediary metabolism by amiodarone in dog thyroid slices.
Amiodarone, an iodine-containing antiarrhythmic drug, has been reported to interfere with thyroid function and thyroid hormone metabolism. We studied the effects of amiodarone on basal and agonist [thyroid-stimulating hormone (TSH), phorbol ester, or carbachol]-stimulated glucose oxidation, 32PO4 incorporation into phospholipids, and adenosine 3',5'-cyclic monophosphate (cAMP) concentration in dog thyroid slices. Slices were preincubated with amiodarone at 37 degrees C for 1 h before the addition of agonist and the appropriate radioisotope. cAMP stimulation was measured after 20 min, glucose oxidation for 45 min, and 32PO4 incorporation into phospholipids for 2 h. Amiodarone (0.5 mM) had no effect on basal 14CO2 formation or 32PO4 incorporation into phospholipids but significantly inhibited TSH, phorbol ester, and carbachol stimulation of these parameters. It also inhibited cAMP stimulation by TSH. Inhibition of TSH-stimulated [14C]glucose oxidation was also obtained with another iodide-containing compound, iopanoic acid (0.5 mM), but not with iothalamate (up to 10 mM). Inhibition by amiodarone was still present, but to a lesser extent, when it was added at the same time as the agonist. Inhibition of stimulated [14C]glucose oxidation persisted even after the slices were incubated without amiodarone for 6 h. Inhibition by amiodarone, in contrast to that by inorganic iodide, was not prevented by 1 mM methimazole added at the same time as amiodarone. These results indicate that the inhibitory effects of amiodarone on thyroid function are not due to dissociation of iodide from the molecule.
Pasquali
D
D
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
Tseng
F Y
FY
Rani
C S
CS
Field
J B
JB
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002250:Carbon Radioisotopes; D004285:Dogs; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D066298:In Vitro Techniques; D007480:Iopanoic Acid / Q000494:pharmacology; D007483:Iothalamic Acid / Q000494:pharmacology; D007700:Kinetics; D010710:Phosphates / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology
D002250:Carbon Radioisotopes; D010710:Phosphates; D010761:Phosphorus Radioisotopes; D007483:Iothalamic Acid; D002217:Carbachol; D013972:Thyrotropin; D007480:Iopanoic Acid; D005947:Glucose; D000638:Amiodarone; D013755:Tetradecanoylphorbol Acetate