Davies T F, McLachlan S M, Povey P M, Smith B R, Hall R
Endocrinology. 1977 Apr;100(4):974-9. doi: 10.1210/endo-100-4-974.
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.
普萘洛尔是一种β肾上腺素能阻断药物，已知它能抑制促甲状腺素（TSH）对甲状腺膜中腺苷-3',5'-单磷酸（环磷酸腺苷）生成的刺激作用，但这种抑制作用的机制尚不清楚。因此，我们研究了普萘洛尔对125I标记的TSH与人甲状腺膜结合的影响。结果发现，d-普萘洛尔和l-普萘洛尔均能增强125I标记的TSH与甲状腺膜的结合。结合的标记量从无普萘洛尔时的约30%增加到存在3.3×10(-3)M普萘洛尔时的约60%。对结合数据进行Scatchard分析表明，普萘洛尔增加了促甲状腺素-促甲状腺素受体相互作用的结合常数。醋丁洛尔、碳酸锂、甲巯咪唑和生长抑素对促甲状腺素结合无影响。普萘洛尔的这种作用似乎是由于其对甲状腺膜的直接可逆作用，可能归因于该药物的膜破坏特性而非其β阻断活性。TSH-甲状腺膜相互作用结合常数增加导致TSH受体占有率增加，这与TSH刺激的环磷酸腺苷生成减少相对应。这些数据可能表明普萘洛尔降低了受体-腺苷酸环化酶偶联系统的效率。
