Characterization of adenosine receptors involved in adenosine-induced bronchoconstriction in allergic rabbits.
1. Recent work has suggested that adenosine may be involved in asthma via the activation of A1 receptors. However, the role of the recently cloned A3 receptor in airways is largely unknown. In the present study, we have investigated the role of the A3 receptor in adenosine-induced bronchoconstriction in allergic rabbits. 2. Aerosol challenge of antigen (Ag) immunized rabbits with the adenosine precursor, adenosine 5'-monophosphate (AMP), resulted in a dose-dependent fall in dynamic compliance (Cdyn). The maximum fall in Cdyn in these rabbits was significantly greater than that in litter matched, sham immunized animals (P < 0.05). However, there was no significant difference in the maximum increase in airways resistance (Rt) between Ag and sham immunized rabbits (P > 0.05). 3. Aerosol challenge of Ag immunized rabbits with cyclopentyl-adenosine (CPA) (A1-receptor agonist) elicited a dose-dependent fall in Cdyn in Ag immunized rabbits and the maximum fall in Cdyn in these rabbits was significantly greater than that observed in sham immunized rabbits (P < 0.05). Similarly, CPA induced dose-dependent increases in R1 in Ag immunized rabbits whereas sham immunized rabbits failed to respond to CPA within the same dose range. The maximum increase in RL in Ag immunized rabbits was significantly greater than that of sham immunized rabbits (P < 0.05). 4. Aerosol challenge of either Ag or sham immunized rabbits with the A3 agonist aminophenylethyladenosine (APNEA) did not elicit dose-dependent changes in either RL or Cdyn. Moreover, there was no significant difference in the maximum response, measured by either parameter, between the two animal groups (P > 0.05). 5. These data provide further evidence for a role of the A1 receptor in the airways, but do not support a role for the A3 receptor in adenosine-induced bronchoconstriction in the allergic rabbit.
el-Hashim
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Sackler Institute of Pulmonary Pharmacology, Kings College, University of London.
D'Agostino
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Matera
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D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000249:Adenosine Monophosphate / Q000494:pharmacology; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D005260:Female; D006967:Hypersensitivity / Q000503:physiopathology*; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D011817:Rabbits; D018047:Receptors, Purinergic P1 / Q000502:physiology*
C086112:N(6)-2-(4-aminophenyl)ethyladenosine; D018047:Receptors, Purinergic P1; C048599:N(6)-cyclopentyladenosine; D000249:Adenosine Monophosphate; D000241:Adenosine