Adenosine receptor-mediated bronchoconstriction and bronchial hyperresponsiveness in allergic rabbit model.
Recently, there has been an increasing interest in adenosine as a potential mediator of allergic asthma. In the present study, we have employed an allergic rabbit model of late-phase asthma to characterize the adenosine receptor subtype in the asthmatic airways. The allergic rabbit model has physiological characteristics and pharmacological sensitivity comparable to human asthma. Adenosine causes a dose-dependent bronchoconstriction in allergic, but not in normal, rabbits. This adenosine-induced bronchoconstriction is significantly inhibited by theophylline, an adenosine receptor antagonist, thus suggesting the involvement of adenosine receptor(s). 5'-(N-ethylcarboxyamido) adenosine (NECA), a nonselective agonist, 2-[p-(2-carboxyethyl)-phenethylamino]-5'-(N-ethylcarboxamido)-aden osine (CGS-21680), an A2-selective receptor agonist, and cyclopentyl adenosine (CPA), an A1-selective agonist, were used to characterize the adenosine receptor subtype in the airways of allergic rabbits, respectively. The PC50 (concentration of agonist in mg/ml required to reduce the dynamic compliance 50% from the baseline) values for adenosine, CGS-21680, NECA, and CPA were 9.25 +/- 0.86, 6.8 +/- 0.69, 3.90 +/- 0.27, and 1.45 +/- 0.26 mg/ml, respectively. Thus the potency profile for the bronchoconstrictor of adenosine in this model is a typical A1-receptor subtype (CPA > NECA > CGS-21680 > adenosine). Adenosine also induced further bronchial hyperresponsiveness (BHR) at 1 but not at 24 h following aerosol challenge.(ABSTRACT TRUNCATED AT 250 WORDS)
Ali
S
S
Department of Medicine, School of Medicine, East Carolina University, Greenville, North Carolina 27858.
Mustafa
S J
SJ
Metzger
W J
WJ
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D004391:Dust; D007114:Immunization; D008925:Mites / Q000276:immunology; D011817:Rabbits; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D012130:Respiratory Hypersensitivity / Q000503:physiopathology*; D013806:Theophylline / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D004391:Dust; D018047:Receptors, Purinergic P1; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine; D013806:Theophylline; D000241:Adenosine