The influence of propranolol on the thyrotropin receptor.
Propranolol, a beta adrenergic blocking drug, is known to inhibit the thyrotropin (TSH) stimulation of adenosine-3',5'-monophosphate (cyclic AMP production in thyroid membranes but the mechansim of this inhibitory action is known. We have therefore investigated the influence of propranolol on the binding of 125I-labelled TSH to human thyroid membranes. Both d- and l-propranolol were found to enhance the binding of 125I-labelled TSH to thyroid membranes. The amount of label bound increased from about 30% in the absence of propranolol to about 60% in the presence of 3.3 x 10(-3)M propranolol. Scatchard analysis of the binding data indicated that propranolol increased the association constant of the thyrotropin-thyrotropin receptor interaction. Practolol, lithium carbonate, methimazole, and somatostatin had no effect on thyrotropin binding. This effect of propranolol appeared to be due to a direct reversible action of propranolol on the thyroid membranes and could be attributed to the membrane-disrupting properties of the drug rather than its beta-blocking activity. The increased TSH receptor occupancy which resulted from the increased association constant of the TSH-thyroid membrane interaction corresponded with a decrease in TSH-stimulated cyclic AMP formation. These data could indicate that propranolol reduced the efficiency of the receptor-adenylyl cyclase coupling system.
D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D011433:Propranolol / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects*; D013237:Stereoisomerism; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism*
D011956:Receptors, Cell Surface; D013972:Thyrotropin; D011433:Propranolol; D000242:Cyclic AMP