Specific and non-specific effects of beta-adrenoceptor agonists on guinea pig alveolar macrophage function.
The existence of beta-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 Kd 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 beta 2-subtype. The cyclic AMP levels of alveolar macrophages could be increased by selective beta 2-adrenoceptor agonists but not by selective beta 1-adrenoceptor agonists. The influence of non-selective beta- and selective beta 1- and beta 2-adrenoceptor agonists on the phagocytic and metabolic responsiveness of alveolar macrophages was also studied. Addition of beta-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 beta 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 beta 2-receptor agonists, salbutamol and terbutaline, had no effect on the oxidative metabolism of alveolar macrophages. We conclude that guinea pig alveolar macrophages possess beta 2-adrenoceptors on their cell surface and that these receptors are not involved in the phagocytic activity of alveolar macrophages.
Henricks
P A
PA
Department of Veterinary Pharmacology, State University of Utrecht, The Netherlands.
Van Esch
B
B
Van Oosterhout
A J
AJ
Nijkamp
F P
FP
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D020120:Iodocyanopindolol; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D010587:Phagocytosis / Q000187:drug effects; D010869:Pindolol / Q000031:analogs & derivatives; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D020120:Iodocyanopindolol; D006861:Hydrogen Peroxide; D010869:Pindolol; D000242:Cyclic AMP