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

Abstract

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)