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1 Inhaled adenosine induces airway obstruction in asthmatic but not healthy subjects, a phenomenon that is also observed in various animal species when they are immunised to a relevant antigen, but which does not occur in naı¨ve animals. The purpose of this study was to investigate the mechanisms of airway responsiveness to adenosine receptor agonists in anaesthetised allergic guinea pigs. 2 Inhaled adenosine 5 0 -monophosphate (AMP), the A 1 -selective adenosine receptor agonist N 6 -cyclopentyladenosine (CPA) and ovalbumin all caused airway obstruction in allergic guinea pigs, but not naı¨ve animals, as assessed by changes in total lung resistance. In contrast, the A 2a -selective (CGS 21680; 2-p-(2-carboxyethyl)phenethylamino-5 0 -N-ethylcarboxoamido adenosine) and A 3 -selective (IB-adenosine receptor agonists failed to elicit airway obstruction in passively sensitised guinea pigs. 3 Airway obstruction induced by AMP or CPA was not inhibited by the H 1 receptor antagonist, mepyramine (1 mg kg À1 ) in passively sensitised guinea-pigs. In contrast, airway obstruction to ovalbumin was significantly inhibited by this antagonist. 4 Airway obstruction induced by AMP and CPA was significantly inhibited in sensitised animals chronically treated with capsaicin. In contrast, airway obstruction to ovalbumin was not inhibited by this treatment. 5 Airway obstruction induced by AMP, CPA and ovalbumin was significantly inhibited following bilateral vagotomy or pharmacological treatment with atropine (2 mg kg À1 ). 6 Airway obstruction to CPA was inhibited by the adenosine A 1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX: 0.1-1 mg kg À1 ). In contrast, airway obstruction to ovalbumin was not inhibited by this treatment. 7 These observations provide evidence indicating that AMP and CPA may induce airway obstruction in sensitised guinea pigs by a mechanism unrelated to histamine release from mast cells, but is mediated via an adenosine A 1 -receptor-dependent mechanism. The inhibition of AMP-and CPA-induced airway obstruction by atropine, capsaicin and bilateral vagotomy suggests a neuronaldependent mechanism with the particular involvement of capsaicin-sensitive nerves.

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