Epithelium-dependent relaxation of guinea-pig tracheal smooth muscle by histamine: evidence for non-H1- and non-H2-histamine receptors.

Epithelium-dependent modulation of the effect of histamine on airway smooth muscle of guinea-pig was studied by using the coaxial bioassay system. Histamine-induced contraction was followed by epithelium-dependent relaxation in the presence of indomethacin, propranolol, atropine and cimetidine. Mepyramine failed to prevent histamine-induced epithelium-dependent relaxation of carbachol-precontracted tracheal smooth muscle in the presence of cimetidine. This relaxant response could be prevented by an H3-histamine receptor antagonist, thioperamide. An agonist, (R) alpha-methylhistamine, of novel (H3)-histamine receptors was found ineffective to produce epithelium-dependent relaxation. It is concluded that the stimulation of non-H1- and non-H2-histamine receptors of guinea-pig airway epithelial cell layer takes part in the release of (a) relaxant factor(s), which counteracts, H1-histamine receptor-mediated bronchoconstriction.