Leukotriene D4 potentiates histamine-induced bronchoconstriction in guinea-pigs.
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 micrograms/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.
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects*; D004357:Drug Synergism; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects; D013189:SRS-A / Q000494:pharmacology*; D014628:Vagotomy
D013189:SRS-A; D001285:Atropine; D006632:Histamine; D007213:Indomethacin