Contractile responses to adenosine, R‐PIA and ovalbumen in passively sensitized guinea‐pig isolated airways

Responses to adenosine, R‐PIA and ovalbumen were examined in guinea‐pig isolated superfused tracheal spirals to determine the effects of passive sensitization by overnight incubation in serum from ovalbumen (OA)‐sensitized or non‐sensitized guinea‐pigs. Tissues incubated with serum from non‐sensitized and OA‐sensitized guinea‐pigs contracted (0.07±0.02 and 0.04±0.01 g, respectively) to adenosine (300 μM) whereas non‐incubated or Krebs‐incubated tissues produced no contractions to adenosine or ovalbumen (10 μg). Ovalbumen caused substantial contractions (0.40±0.09 g) after OA‐sensitized serum incubation and significantly (P<0.05) smaller contractions (0.08±0.03 g) after non‐sensitized serum incubation. Tracheae from guinea‐pigs actively sensitized to ovalbumen 14–21 days beforehand also contracted to adenosine, R‐PIA (3 μM) and ovalbumen. The A1/A2 adenosine receptor antagonist, 8‐phenyltheophylline (8‐PT, 3 μM), failed to antagonize these contractions, suggesting that A1/A2 adenosine receptors were not involved. Unlike adenosine, R‐PIA (3 μM) produced contractions in non‐incubated (0.23±0.04 g) or Krebs‐incubated (0.15±0.04 g) tracheae, as well as after passive and active sensitization. None of these responses were blocked by 8‐PT. The A3 receptor agonist, IB‐MECA, in the presence of 8‐PT produced small contractions in passively sensitized tracheae (10 μM, 0.02±0.003 g) and, in larger doses (100 μM and 1 mM), contracted actively sensitized tracheae. In actively sensitized trachea, the A3 receptor antagonist, MRS‐1220 (100 nM), significantly (P<0.05) attenuated adenosine contractions in the presence of 8‐PT from 0.23±0.07 g to 0.07±0.03 g. These results show that passive, like active sensitization, reveals bronchoconstrictions to adenosine of isolated tracheae. The insensitivity to 8‐PT blockade, the antagonism by MRS‐1220, and the fact that the A3 receptor agonist, IB‐MECA, mimics this response, suggest involvement of A3 receptors. R‐PIA, however, has a different profile of adenosine receptor activity. British Journal of Pharmacology (2002) 137, 729–738. doi:10.1038/sj.bjp.0704902