Bronchodilatation of guinea-pig perfused bronchioles induced by the H3-receptor for histamine: role of epithelium. |
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Authors: | J. L. Burgaud and N. Oudart |
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Affiliation: | Laboratoire de Pharmacologie, UFR de Pharmacie, Limoges, France. |
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Abstract: | 1. The influence of epithelium on the effects of H3-histamine receptor agonist (R)alpha-methylhistamine [(R)alpha-MeHist] on airways was investigated on the guinea-pig perfused bronchioles. 2. 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. 3. In this preparation (R)alpha-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. 4. 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 x 10(-5) M NG-nitro-L-arginine methyl ester (an inhibitor of NO synthesis). 5. It is suggested that, in guinea-pig perfused bronchioles (R)alpha-MeHist induces an epithelium-dependent relaxation via the release of metabolite(s) of arachidonic acid. |
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