EFFECTS OF CROMAKALIM (BRL-34915) IN TRACHEA ISOLATED FROM ACTIVELY SENSITIZED GUINEA-PIGS

The effects of cromakalim were examined in tracheal strips isolated from normal (unsensitized) guinea-pigs and from animals actively sensitized to bovine serum albumin. Sensitized tracheae exhibited hyper-responsiveness to KCl, acetylcholine and histamine. In normal and sensitized tracheae, cromakalim (0.01-10 muM) produced a concentration-related suppression of spontaneous tone. The ability of cromakalim to relax tracheal strips was reduced when tone was raised by KCl (25 mM), acetylcholine (0.1 mm) or histamine (0.1 mM) and lost against KCl (120 mM)-induced spasm. Procaine (5 mM) abolished the relaxant effect of cromakalim whilst tetraethylammonium (8 mM) was without effect. These effects were similar in normal and sensitized tissues. Cromakalim (10 muM) produced minor alterations of the concentration-effect curves of KCl (1-100 mM), acetylcholine (1 nM-1 mM) and histamine (1 nM-1 mM) in normal and sensitized tissues. The results from this pharmacomechanical study do not support the hypothesis that altered properties of cromakalim-sensitive K+ channels underlie the airway hyper-reactivity induced by active sensitization to bovine serum albumin.