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 from ovalbumin-sensitized guinea pigs were set up. Adenosine and the analogues, 5'-(N-ethylcarboxamido)adeno sine (NECA), R-N-6-phenylisopropyladenosine (R-PIA), 2-chloroadenosine, N-6-2-(4-aminophenyl)ethyladenosine (APNEA) and 5'-AMP yielded bronchoconstrictor responses as increases in perfusion pressure or of tension, respectively, of these two preparations. These responses were greater in tissues from sensitized compared with un-sensitized guinea pigs. Cross-tachyphylaxis occurred between the constrictor responses to adenosine and the other constrictor adenosine agonists which indicated a common site of action. The adenosine transport inhibitors, dipyridamole and S-(p-nitrobenzyl)-6-thioinosine (NBTI), inhibited the constrictor responses to adenosine and the analogues, except 2-chloroadenosine. This was attributed to a potentiation of the opposing relaxant effects which generally occurred at higher concentrations of the agonists. The P-1 purinoceptor antagonists 8-phenyltheophylline and 8-cyclopentyltheophylline (A(1) receptor selective) failed to remove the constrictor responses to adenosine either alone or in the presence of dipyridamole. This suggests that the bronchoconstrictor response of sensitized airways tissues is mediated via the novel xanthine-resistant A(3) receptor.