ANALYSIS OF THE BRONCHOCONSTRICTOR RESPONSES TO ADENOSINE RECEPTOR AGONISTS IN SENSITIZED GUINEA-PIG LUNGS AND TRACHEA

Airway perfused lungs and half-lungs and superfused tracheal spirals f rom ovalbumin-sensitized guinea pigs were set up. Adenosine and the an alogues, 5'-(N-ethylcarboxamido)adeno sine (NECA), R-N-6-phenylisoprop yladenosine (R-PIA), 2-chloroadenosine, N-6-2-(4-aminophenyl)ethyladen osine (APNEA) and 5'-AMP yielded bronchoconstrictor responses as incre ases in perfusion pressure or of tension, respectively, of these two p reparations. These responses were greater in tissues from sensitized c ompared with un-sensitized guinea pigs. Cross-tachyphylaxis occurred b etween the constrictor responses to adenosine and the other constricto r adenosine agonists which indicated a common site of action. The aden osine transport inhibitors, dipyridamole and S-(p-nitrobenzyl)-6-thioi nosine (NBTI), inhibited the constrictor responses to adenosine and th e analogues, except 2-chloroadenosine. This was attributed to a potent iation of the opposing relaxant effects which generally occurred at hi gher concentrations of the agonists. The P-1 purinoceptor antagonists 8-phenyltheophylline and 8-cyclopentyltheophylline (A(1) receptor sele ctive) failed to remove the constrictor responses to adenosine either alone or in the presence of dipyridamole. This suggests that the bronc hoconstrictor response of sensitized airways tissues is mediated via t he novel xanthine-resistant A(3) receptor.