Mechanisms Of Adenosine-Induced Bronchoconstriction - An Animal-Model

A rat model of adenosine-induced bronchoconstriction has been used to study the mechanisms involved in the adenosine-induced airway narrowing. A remarkable difference in bronchial responsiveness to adenosine between various inbred rat strains was observed. The BDE strain was the most responsive strain and was used for further characterization of the adenosine response in the airways. Tachyphylaxis to a second challenge was a constant phenomenon. The order of potency of adenosine analogues was 5'N-ethoxycarboxy-adenosine (NECA) > adenosine > N6-(2-phenylisopropyl)-adenosine (R-PIA). The adenosine-induced bronchoconstriction was mainly caused by the activation of mast cells and postganglionic vagal neurons. The direct effect of adenosine on bronchial smooth muscle was rather limited. Adenosine challenge induced the release of histamine and 5-hydroxytryptamine in the airways. Cromoglycate, nedocromil, theophylline, and enprofylline inhibited the adenosine-induced bronchoconstriction. Adenosine and neurokinin A had an additive and possibly a synergistic effect in causing bronchoconstriction and mast cell activation.