Propranolol increases binding of thyrotropin to thyroid membranes

Abstract

β-ADRENERGIC antagonists such as propranolol possess two pharmacologically relevant properties—β-adrenergic blockade is observed at relatively low concentrations, whilst at higher concentrations they are effective membrane stabilising agents^1,2. The latter property which, unlike β-adrenergic antagonism is non-stereospecific, is also described as local anaesthetic or quinidine like activity and it possibly accounts at least in part, for the anti-arrhythmic properties of propranolol—local anaesthetics and quinidine also showing anti-arrhythmic activity^3–5. A wide variety of effects have been associated with local anaesthetic activity¹, but as yet there is no unifying explanation of the mechanism of action. We have investigated the effect of propranolol, acting in its capacity as a local anaesthetic, on a hormone receptor adenylate cyclase system which might be expected to be sensitive to membrane perturbation by local anaesthetics, and reported inhibition of thyrotropin (TSH) stimulation of adenylate cyclase in thyroid plasma membranes⁶. We present here a study of the consequence of local anaesthetic activity on binding of the hormone to membrane-associated receptors, and in this respect contrast the local anaesthetic activity of propranolol with that of local anaesthetics such as xylocaine or procaine.