CHANGES IN THE DENSITY OF BETA-ADRENERGIC RECEPTORS IN RAT LYMPHOCYTES, HEART AND LUNG AFTER CHRONIC TREATMENT WITH PROPRANOLOL

Abstract

Abrupt withdrawal after the chronic administration of propranolol results in clinical syndromes that suggest adrenergic hypersensitivity. Propranolol administration may lead to an increase in the density of .beta. adrenergic receptors on human lymphocytes. The relevance of changes measured by lymphocytes to changes that may occur in solid tissues were assessed. Direct measurement of the density and properties of .beta. adrenergic receptors in membrane fragments was performed in vitro using the radioligand [125I]iodohydroxybenzylpindolol. Chronic infusion of propranolol by s.c. implanted osmotic minipumps generated sustained plasma concentrations of propranolol sufficient to cause chronic blockade of .beta. adrenergic receptors. Infusion of propranolol for 7 days resulted in significant increases in the density of .beta. adrenergic receptors in rat ventricles, lungs and lymphocytes. A computer-assisted graphic analysis of results obtained in studies with drugs selective for .beta.-1 or .beta.-2 receptors revealed increases in the densities of both .beta.-1 and .beta.-2 adrenergic receptors. Changes in .beta. adrenergic receptors on lymphocytes evidently are qualitatively similar to alterations in .beta. adrenergic receptors in solid tissues not routinely accessible in humans. Increases in the densities of .beta.-1 and/or .beta.-2 adrenergic receptors in solid tissues may be related to some of the untoward effects observed in humans after abrupt discontinuation of propranolol administration.