Quantitative Comparison of Bromoacetylated Derivatives of Alprenolol and Pindolol on Beta-Adrenergic Receptor Binding and Mobility in S49 Cells

Abstract

The reactivities with β-adrenergic receptors of the bromoacetyl derivatives of the β-adrenergic antagonists alprenolol and pindolol, BAAM and BIM, respectively, were compared in intact S49 mouse lymphoma cells. Both compounds caused irreversible blockade of receptors and changes in the mobility of the remaining non-modified receptors. BIM proved to be an irreversible blocker of high potency, with an IC₅₀ of 40–60 nM at 4°C, whereas the IC₅₀ for BAAM was 600–900 nM. Moreover, treatment with both compounds resulted in an inhibition of internalization of non-modified receptors (IC₅₀ = 200–300 nM for both). After treatment of desensitized cells which have internalized 50–60 % of their surface receptors, with BIM or BAAM, receptor reappearance was found to be slowed down (IC₅₀ about 100 nM for both compounds). The effects of the bromoacetylated antagonists on receptor internalization were apparently selective for β-adrenergic receptors, since binding and internalization of transferrin or low-density lipoprotein were not affected.