Antigen challenge modifies the cyclic AMP response of inflammatory mediators and beta-adrenergic drugs in alveolar macrophages.
Adenylate cyclase activity was determined in alveolar macrophages (AMs) obtained from bronchoalveolar lavage (BAL) fluids of naive and antigen-challenged guinea pigs. After the anaphylactic reaction in ovalbumin-sensitized guinea pigs, the basal levels of cyclic AMP in AMs were significantly increased compared to the levels in naive AMS (1.87 +/- 0.22 versus 5.26 +/- 0.45 pmol cyclic AMP/5.10(6) cells). Prostaglandin E2 (PGE2), prostacyclin (DC-PGI2), histamine, isoprenaline and salbutamol stimulated adenylate cyclase activity more effectively in AMs obtained from sensitized guinea pigs after the booster injection compared to AMs obtained from non-treated animals. Moreover, DC-PGI2 and histamine, which were hardly able to induce a rise in cyclic AMP levels in naive AMs, become effective activators in AMs obtained after antigen challenge (100 and 60% increase in the response, respectively). Using selective receptor ligands, we have shown that beta 2-adrenoceptors and H2-subtype histamine receptors are functionally coupled to macrophage adenylate cyclase activity. The present data indicate that sensitization does not affect the configuration of the receptor on the outer membrane (no change in affinity constants), but affects other parts of the transmembrane signal system leading to the intracellular production of cyclic AMP (e.g. regulatory binding proteins or increases in the number of receptors).
Beusenberg
F D
FD
Department of Pharmacology, Faculty of Medicine, Erasmus University Rotterdam, The Netherlands.
Adolfs
M J
MJ
Van Schaik
A
A
Van Amsterdam
J G
JG
Bonta
I L
IL
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone / Q000502:physiology; D011464:Epoprostenol / Q000502:physiology; D006168:Guinea Pigs; D007249:Inflammation / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010047:Ovalbumin / Q000276:immunology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000941:Antigens; D010047:Ovalbumin; D011464:Epoprostenol; D000242:Cyclic AMP; D015232:Dinoprostone; D007545:Isoproterenol; D000420:Albuterol