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.