Effects of chronic administration of agonists and antagonists on the density of beta-adrenergic receptors

It is frequently hypothesized that drug-induced alterations in the density of β-adrenergic receptors underlie tolerance to and physical dependence on agonists and antagonists at β-adrenergic receptors. Two approaches to determining the effect of treatment with drugs on the density of β-adrenergic receptors are described. In the first, the density of β-adrenergic receptors was measured on leukocytes taken from human subjects during and after drug treatment. Treatment with the antagonist propranolol caused an increase in the density of β-adrenergic receptors on leukocytes, whereas treatment with the agonists terbutaline and ephedrine, or pindolol, an antagonist with intrinsic sympathomimetic activity, caused a decrease in the density of β-adrenergic receptors. In the second approach, the effect of agonists on the density of β-adrenergic receptors on C₆ glioma cells in culture was determined. Incubation with the full agonist isoproterenol decreased the density of both β₁ and β₂-adrenergic receptors. In contrast, incubation with pindolol or celiprolol, also an antagonist with intrinsic sympathomimetic activity, selectively decreased the density of β₂-adrenergic receptors. Pindolol and celiprolol may be useful in situations in which selective stimulation of β₂-adrenergic receptors and blockade of β₁-adrenergic receptors is desirable.