Mediators of adenosine- and ovalbumen-induced bronchoconstriction of sensitized guinea-pig isolated airways

The mediators of bronchoconstriction of isolated lungs and trachea from ovalbumen sensitized guinea-pigs to adenosine and ovalbumen were examined using relevant antagonists. Changes in perfusion pressure and tension of paired lung halves and tracheal spiral strips, respectively, were recorded in response to adenosine (1 mM lung, 300 microM trachea), histamine (10 microM), methacholine (10 microM) and ovalbumen (10 microg). One half was perfused with antagonist while the other received vehicle. Tracheal strips were superfused throughout with the P(1) receptor antagonist 8-phenyltheophylline, to examine 8-phenyltheophylline-resistant responses. The histamine H(1) receptor antagonist, mepyramine (1.5 mM), the cyclooxygenase inhibitors, indomethacin (5 mM) and diclofenac (5 mM), the leukotriene receptor antagonist, zafirlukast (1 mM), and the lipoxygenase inhibitor, zileuton (20 mM), alone failed to inhibit bronchoconstriction by adenosine and ovalbumen of the lung and trachea. When two antagonists were combined, only mepyramine and zafirlukast significantly reduced the lung responses to adenosine and ovalbumen. The tracheal adenosine response was substantially reduced, although not significantly, while ovalbumen was significantly reduced. When mepyramine, indomethacin and zafirlukast were combined, the lung constriction by adenosine and ovalbumen were virtually abolished. Similarly, the combination of mepyramine, diclofenac and zafirlukast significantly attenuated the lung responses to adenosine and ovalbumen. Thus, histamine, cyclooxygenase products and leukotrienes alone are not responsible for the bronchoconstriction of isolated sensitized lung tissues to adenosine or ovalbumen, which appears to be due to the release of all three mediators.