Propranolol has direct antithyroid activity: inhibition of iodide transport in cultured thyroid follicles.
The effect of propranolol on the process of thyroid hormone formation was studied in a physiological culture system. Porcine thyroid follicles were preincubated with propranolol for 24 h. Iodide transport, iodine organification, and de novo thyroid hormone formation were measured by incubating these follicles with the mixture of carrier-free 0.1 microCi Na125I and 50 nM NaI for 2 to 6 h at 37 degrees C. A concentration of propranolol greater than 100 microM inhibited iodide transport in a dose-dependent manner; this inhibition was non-competitive with iodide and independent of thyrotropin (TSH). Reduced iodine organification and thyroid hormone formation was seen with 150 microM propranolol or greater. The inhibitory action of propranolol was not caused by beta-blocking activity, since D-propranolol (devoid of beta-blocking activity) inhibited iodide transport, and other beta-blockers (metoprolol, atenolol, and labetalol) did not inhibit iodide transport. The inhibition of iodide transport was most likely caused by membrane stabilizing activity since quinidine, which possesses the same membrane stabilizing activity as propranolol, also inhibited iodide transport. TSH-mediated cAMP generation and Na+K+ ATPase activity, membrane functions for iodide transport, were unaffected by propranolol. Our study has shown, for the first time, that propranolol has a direct antithyroid action, namely inhibition of iodide transport in the intact thyroid follicle.
Murakami
S
S
Division of Endocrinology and Metabolism, Research and Medical Services, Veterans Affair, West Los Angeles Medical Center, CA.
Nasu
M
M
Fukayama
H
H
Krishnan
L
L
Sugawara
M
M
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D007454:Iodides / Q000378:metabolism*; D007470:Monoiodotyrosine / Q000096:biosynthesis; D011433:Propranolol / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis; D013237:Stereoisomerism; D013552:Swine; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism; D013963:Thyroid Hormones / Q000096:biosynthesis; D013972:Thyrotropin / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D007454:Iodides; D013963:Thyroid Hormones; D013972:Thyrotropin; D011433:Propranolol; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase; D007470:Monoiodotyrosine