AJP - Lung Cellular and Molecular Physiology, Vol 266, Issue 3 271-L277, Copyright © 1994 by American Physiological Society

ARTICLES

Adenosine receptor-mediated bronchoconstriction and bronchial hyperresponsiveness in allergic rabbit model

S. Ali, S. J. Mustafa and W. J. Metzger
Department of Medicine, School of Medicine, East Carolina University, Greenville, North Carolina 27858.

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)

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