The tracheal tone is influenced by histaminergic receptors and by the epithelium derived relaxing factor (EpDRF) which contains metabolites of arachidonic acid. The aims of the present study were the following: 1) to investigate the role of Hi- and Нз-receptors in the tracheal tone regulation using as test substances histamine (H), the Hi-receptor antagonist mepyramine and the Нз-receptor agonist (R)a-methylhistamine [(R)a -MHA]; 2) to study the influence of the cyclooxygenase (COX) inhibitor indomethacin on the tracheal responsiveness to the examined substances. The experiments were carried out on isolated guinea-pig tracheal rings. Histamine at cumulative concentrations contracts the trachea. In the presence of mepyramine the concentration- response curves to H are shifted to the right that proves the concept of the Hi-receptor mediated tracheal contraction. In the presence of indomethacin the concentration-response curves to H are shifted to the left and the maximal contraction is significantly increased due to the inhibition of the COX pathway. (R)oc-MHA at concentrations up to lxlfH M leads to a slight tracheal contraction, which is probably Hi-receptor mediated as it is reduced in the presence of mepyramine. The ЗхКИ M concentration of (R)a-MHA relaxes the trachea probably due to its Нз-receptor agonistic activity. In the presence of indomethacin this relaxation is turned to a further contraction. After tracheal precontraction by H, (R)a-MHA concentration dependently relaxes the trachea. This spasmolytic effect is insignificantly influenced by mepyramine and is almost completely abolished in the presence of indomethacin, which shows that it is probably due to an increased production of metabolites of arachidonic acid.
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