Leukotriene D4 potentiates histamine-induced bronchoconstriction in guinea-pigs

Abstract

Histamine concentration-response curves performed on isolated airways smooth muscle preparations were unaffected by threshold constrictor concentrations of LTD₄ (194±34 pM for parenchymal strips and 1940±480 pM for isolated trachea, respectively). In contrast, LTD₄, when administered between 2 and 60 s beforehand, potentiated bronchoconstrictor responses to histamine in anaesthetized, artificially ventilated guinea-pigs. Doses of LTD₄, which did not produce direct effects on airways resistance, potentiated histamine-induced bronchoconstriction to a lesser degree than those having small direct effects. This potentiation was prevented by bilateral vagotomy. In addition, the antagonists atropine (100 μg/kg), FPL55712 (5 mg/kg) and indomethacin (1 mg/kg) effectively prevented the interaction. It is suggested that the interaction between LTD₄ and histamine involves a specific leukotriene receptor, possibly linked to the generation of a cyclo-oxygenase metabolite and requires intact cholinergic innervation of airways smooth muscle. Furthermore, these results are consistent with the hypothesis that LTD₄ may be a mediator of bronchial hyperreactivity.