Effects of CGS 21680, a selective adenosine A2A receptor agonist, on allergic airways inflammation in the rat

We have investigated the effect of 2(4-((2-carboxymethyl)phenyl)ethylamino)-5'-N-ethylcarboxamidoadenosine (CGS 21680), a potent and selective agonist at adenosine A2A receptors, on pulmonary inflammation induced by allergen challenge in the ovalbumin-sensitised, Brown Norway rat. Aerosol administration of ovalbumin (5 mg x ml(-1) for 60 min; calculated dose 0.4 mg x kg(-1)) induced increases in bronchoalveolar lavage fluid leukocyte numbers, protein content and myeloperoxidase and eosinophil peroxidase activities measured 24 h post challenge. CGS 21680 (10 and 100 microg x kg(-1) given intratracheally (i.t.) 30 min before and 3 h after allergen challenge) inhibited dose-dependently all the parameters of inflammation. Qualitatively similar results were obtained with the glucocorticosteroid, budesonide (0.1, 1 and 10 mg x kg(-1) given 3 h prior to ovalbumin challenge). CGS 21680 given i.t. reduced blood pressure in anaesthetised rats at similar doses to those at which anti-inflammatory effects were manifested. Both the anti-inflammatory and hypotensive responses to CGS 21680 were blocked by pretreatment with the selective adenosine A2A receptor antagonist, 4-(2-(7-amino-2-(2-furyl)(1,2,4)triazolo(2,3-a(1,3,5)triazin-5-yl amino)ethyl)phenol (ZM 241385), 3 mg x kg(-1) p.o., 1 h prior to the agonist. Thus, CGS 21680 manifests broad-spectrum anti-inflammatory activity in a model of allergic asthma in the Brown Norway rat through activation of adenosine A2A receptors. The striking similarity to budesonide, a clinically used anti-inflammatory agent, suggests that adenosine A2A receptor agonists may be useful alternatives to glucocorticosteroids in the treatment of asthma.