Adenosine-induced bronchoconstriction and contraction of airway smooth muscle from allergic rabbits with late-phase airway obstruction: evidence for an inducible adenosine A1 receptor.
Recently, there has been an increasing interest in adenosine as a potential mediator of allergic asthma. In the present study, we used the allergic rabbit model developed in our laboratory to study the airway responses to adenosine and receptor binding in allergic lung vs. normal. Neonatal, pathogen-free rabbit litter mates were injected intraperitoneally within 24 hr of birth with ragweed pollen extract (1 mg/ml) to produce preferentially allergen-specific immunoglobulin E. Immunization produced bronchial airway hyperresponsiveness. Aerosolized adenosine (0.156-10 mg/ml) caused a dose-dependent bronchoconstriction (PC50 adenosine = 1.64 +/- 0.84 mg/ml). 9-Chloro-2-(2-furyl)[1,2,4]triazole[1,5- c]quinazolin-5-amine (CGS-15943), a nonxanthine adenosine receptor antagonist, significantly inhibited the adenosine-induced airway obstruction in term of dynamic compliance (P < .05). Adenosine also increased the lung resistance in a dose-dependent manner which was significantly inhibited by CGS-15943 (P < .05). Nonimmunized, pathogen-free, age-matched rabbits (control) did not respond to adenosine at these same concentrations. Adenosine also produced a concentration-dependent (10(-9)-10(-4) M) contraction of isolated tracheal and bronchial airway rings in vitro from allergic rabbits but had no detectable effect on normal rabbit airway smooth muscle. Peripheral airway smooth muscles (secondary and tertiary) were more responsive to adenosine than central (tracheal) airways. The contraction produced by 10(-4) M adenosine in primary, secondary and tertiary airways was 90, 135 and 265% of the contraction produced by 50 mM KCl, respectively. CGS-15943 (10(-7) M) significantly inhibited the adenosine-induced contraction (P < .05) shifting the dose-response curve to the right.(ABSTRACT TRUNCATED AT 250 WORDS)
Ali
S
S
Department of Medicine, School of Medicine, East Carolina University, Greenville, North Carolina.
Mustafa
S J
SJ
Metzger
W J
WJ
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D001667:Binding, Competitive; D016084:Bronchoconstriction / Q000187:drug effects*; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D018047:Receptors, Purinergic P1 / Q000096:biosynthesis*; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D014611:Vaccination; D014970:Xanthines / Q000378:metabolism
D018047:Receptors, Purinergic P1; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine