Specific and non-specific effects of β-adrenoceptor agonists on guinea pig alveolar macrophage function

Abstract

The existence of β-adrenoceptors on guinea pig alveolar macrophage membranes was determined by means of radioligand binding studies. Saturable binding with [ 125I]cyanopindolol demonstrated 38±6 fmol binding sites per 10 6 alveolar macrophages with a K d of 0.85±0.15 nM. With timolol, atenolol and ICI 118.551 for competition of [ 125I]cyanopindolol binding it became clear that guinea pig alveolar macrophages possessed adrenergic binding sites of the β 2-subtype. The cyclic AMP levels of alveolar macrophages could be increased by selective β 2-adrenoceptor agonists but not by selective β 1-adrenoceptor agonists. The influence of non-selective β- and selective β 1- and β 2-adrenoceptor agonists on the phagocytic and metabolic responsiveness of alveolar macrophages was also studied. Addition of β-adrenoceptor agonists had no effect on the uptake of bacteria by alveolar macrophages. Incubation of alveolar macrophages with increasing amounts of non-selective and selective β 1-agonists resulted in a dose-dependent decrease in the detection of hydrogen peroxide released by alveolar macrophages. This effect was due to the scavenging properties of these drugs. The selective β 2-receptor agonists, salbutamol and terbutaline, had no effect on the oxidative metabolism of alveolar macrophages. We conclude that guinea pig alveolar macrophages possess β 2-adrenoceptors on their cell surface and that these receptors are not involved in the phagocytic activity of alveolar macrophages.