CHARACTERIZATION OF THE ADENOSINE RECEPTORS IN THE AIRWAYS

Adenosine causes bronchoconstriction both in vivo and in vitro in huma n asthmatics. In an in vivo rat model of adenosine-induced bronchocons triction, the order of bronchoconstrictor potency of adenosine analogu es was NECA=CPA>APNEA> CHA>R-PIA>CGS21680. This order of potency does not fit with the classical order of potency for a single subtype of ad enosine receptors. The complete lack of bronchoconstrictory activity o f CGS21680 suggests, nevertheless, that the A(2A) receptor subtype is not involved in the adenosine-induced bronchoconstriction. A remarkabl e finding was the dose-response curve to APNEA, which is thought to ha ve some selective activity on the A(3) receptor. The A(2A)-selective a ntagonist KF17837 (10(-7) to 10(-5) mol/kg) had no significant inhibit ory activity on the adenosine-induced bronchoconstriction. The A(1) an tagonists, KF15372 and KW3902, both significantly inhibited the NECA-i nduced bronchoconstriction in BDE rats. We, therefore, conclude that t he adenosine-induced bronchoconstriction in the rat is most likely due to binding of adenosine to different receptor subtypes including the A(1), A(2B) and A(3) subtypes.