Bronchodilatation of guinea‐pig perfused bronchioles induced by the H3‐receptor for histamine: role of epithelium

Abstract

The influence of epithelium on the effects of H3‐histamine receptor agonist (R)α‐methylhistamine [(R)α‐MeHist] on airways was investigated on the guinea‐pig perfused bronchioles. In preparations under resting tone, removal of the bronchiolar epithelium or treatment with the cyclo‐oxygenase inhibitor indomethacin (10−5 m) increased the constriction induced by histamine and acetylcholine in a concentration‐dependent manner without an alteration of the K+‐induced contraction. In this preparation (R)α‐MeHist induced a concentration‐dependent bronchodilatation which was antagonized in a competitive manner by thioperamide (an H3‐antagonist) with a pA2 value of 8.6. This bronchodilatation was reversed to a low concentration‐dependent constriction after either removal of the epithelium or treatment with indomethacin (10−5 m) but was unaffected by both 10−5 m tranylcypromine (an inhibitor of PGI2 synthesis) and 5 × 10−5 m NG‐nitro‐l‐arginine methyl ester (an inhibitor of NO synthesis). It is suggested that, in guinea‐pig perfused bronchioles (R)α‐MeHist induces an epithelium‐dependent relaxation via the release of metabolite(s) of arachidonic acid. 1993 British Pharmacological Society