AJP - Endocrinology and Metabolism, Vol 259, Issue 4 E529-E533, Copyright © 1990 by American Physiological Society
Inhibition of intermediary metabolism by amiodarone in dog thyroid slices
D. Pasquali, F. Y. Tseng, C. S. Rani and J. B. Field
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
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.
