IN-VIVO ROLE OF THE ADENOSINE A(3) RECEPTOR - N-6-2-(4-AMINOPHENYL)ETHYLADENOSINE INDUCES BRONCHOSPASM IN BDE RATS BY A NEURALLY-MEDIATED MECHANISM INVOLVING CELLS RESEMBLING MAST-CELLS

Activation of the adenosine A(3) receptor subtype by the agonist N-6-2 -(4-aminophenyl)ethyladenosine is shown here to induce bronchospasm (i ncreased pulmonary resistance and decreased pulmonary compliance) in B DE strain rats. The effect is substantially reduced by pretreating the rats with compound 48/80, disodium cromoglycate (30 mu g/kg) or epina stine (10 mu g/kg), which is compatible with involvement of mast cells . It is also substantially reduced by combined vagotomy and atropiniza tion or by pretreatment with the NK2 receptor antagonist L-659,877, su ggesting involvement of neuropeptide-mediated neural pathways. The mec hanism by which activation of the adenosine A(3) receptor induces bron chospasm is distinct from the mechanism by which activation of the ade nosine A(1) receptor induces bronchospasm In particular, the A(1) agon ist 2-chloro-N-6-cyclopentyladenosine can increase pulmonary resistanc e independently of mast cell activation. These results are in accord w ith the concept that a pathway exists in vivo by which activation of m ast-like cells can activate axon reflexes, that adenosine acting throu gh its A(3) receptor can potentially up-regulate this pathway and that antiallergic substances such as disodium cromoglycate and epinastine may interfere with this pathway.