Effects of eicosanoids, neuromediators and bioactive peptides on murine airways

The effects of several mediators including prostanoids, neuromediators, bio active peptides and leukotrienes were investigated on the trachea, upper br onchi, lower bronchi and lung parenchyma of selected strains of mice mounte d in a cascade superfusion system. The upper airways (trachea, upper bronch i) responded with greater maxima than lower airways (lower bronchi, lung pa renchyma). Acetylcholine, carbachol, serotonin and 9,11-dideoxy-9 alpha,11 alpha-epoxymethano-prostaglandin F-2 alpha (U-44069) contracted the mouse a irways (acetylcholine > carbachol > serotonin greater than or equal to U-44 069). However, the rank order of potency for these compounds was U-44069 > carbachol > serotonin greater than or equal to acetylcholine. Prostaglandin s E-2, F-2 alpha, and D-2 relaxed the carbachol precontracted isolated mous e airways achieving > 90% relaxation in some cases. The rank order of poten cy for the prostaglandins was E-2 greater than or equal to F-2 alpha > D-2 with the exception of the lower bronchi on which prostaglandins had the fol lowing order of potency: F-2 alpha greater than or equal to E-2 > D-2. The effects of prostaglandins were similar in four commonly used strains of mic e (CD-1, BALB/c, C57BL/c6 and C3H) with some variations in efficacy. Ilopro st was a weak mouse airway relaxant. It had the greatest effect on the trac hea and bronchi of BALB/c and C57BL/c6 mice, whereas it had little or no ef fect on the airways of the CD-1 and C3H mouse strains. Vasoactive intestina l peptide potently relaxed the carbachol and precontracted the mouse trache a and bronchi. However, vasopressin, another bioactive peptide. potently an d efficaciously contracted the mouse trachea and upper bronchi but had litt le effect on the lower bronchi. Vasopressin was the most potent and efficac ious contractile agonist tested in this study. Contractions were observed w ith endothelins-1, -2 and 3 on mouse trachea and bronchi, but marked tachyp hylaxis was present. Sarafotoxin s6c followed the same pattern suggesting t he presence of endothelin ETB receptors on the mouse airways. Of all leukot rienes assayed (B-4, C-4, D-4 and E-4) only leukotriene C-4 weakly contract ed the mouse trachea and upper bronchi, but tachyphylaxis was most evident. (C) 2000 Elsevier Science B.V. All rights reserved.