Action of a novel drug (Zy 16039) on mucus secretion in the ferret isolated trachea in vitro.

1. The effect of 4-H-2-carboxamido-4-phenyl-thieno-[3,2c]-[1]-benzopyran (Zy 16039) was examined on the smooth muscle contraction, mucus secretion and albumin transudation in the ferret whole trachea in vitro. 2. Zy 16039 (0.1-20 microM) produced a concentration-dependent relaxation of the ferret trachea contracted by methacholine (1 microM) and phenylephrine (10 microM). The relaxations were about 20% of the full contractions. 3. Zy 16039 has no effect on the resting (zero) output of mucus in the ferret trachea. Methacholine-induced mucus secretion was significantly inhibited by Zy 16039, whereas phenylephrine-induced secretion was significantly increased. 4. Methacholine-induced secretion of lysozyme, a marker of serous cell secretion, was inhibited by Zy 16039 both with regard to output and concentration of lysozyme. In contrast, Zy 16039 significantly increased the output of lysozyme due to phenylephrine, with no effect on concentration. 5. Zy 16039 had no significant effect on the rate of output of fluorescent albumin through the tracheal wall. However the concentration of albumin in the mucus samples was changed because of the effect of Zy 16039 on mucus secretion induced by methacholine and phenylephrine. 6. We conclude that Zy 16039 relaxes airway smooth muscle, and either promotes or inhibits mucus secretion depending on its source. It has qualitatively similar actions to vasoactive intestinal peptide.