ly-53857 and Airway-Obstruction

Conscious guinea pigs that were briefly exposed to an aerosol of A23187 developed a prolonged airway constrictive response that lasted at least 60 min. Cumulative i.v. doses of various drugs were given and reversal of dynamic compliance (Cdyn) examined. After the final dose of each agent, the animals were killed and excised lung gas volumes, i.e., pulmonary gas trapping, measured. Salbutamol, a beta-2 adrenoceptor agonist; phenidone, a 5-lipoxygenase inhibitor; aminophylline, a methylxanthine bronchodilator; dazoxiben, a thromboxane synthetase inhibitor; REV-6866, a 5-lipoxygenase inhibitor; LY53857, a 5-hydroxytryptamine receptor antagonist; and LY183001, a leukotriene D4/E4 antagonist, partially reversed Cdyn and reduced excised lung gas volume. Atropine, a cholinergic/muscarinic antagonist indomethacin, a cyclooxygenase inhibitor; pyrilamine, a histamine receptor antagonist; and SRI 63-072, a platelet activating factor antagonist, had little or no effect. For all animals, final Cdyn values were highly correlated with reduction of pulmonary gas trapping (r = -0.86, P less than .0001). We conclude that smooth muscle contraction is important in A23187-induced airway obstruction; 5-hydroxytryptamine, thromboxane A2 and lipoxygenase products may be involved in maintaining this response; and that this approach is useful for investigating reversal of ongoing airway constriction.

Topics: Airway Obstruction; Airway Resistance; Albuterol; Animals; Calcimycin; Dose-Response Relationship, Drug; Ergolines; Guinea Pigs; Leukotrienes; Lung Compliance; Male; Platelet Activating Factor; Serotonin; Thromboxane A2