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Lipoxygenase metabolites mediate increased airways resonsiveness to histamine after acute platelet activating factor exposure in the guinea-pig

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Abstract

Platelet activating factor (Paf, 0.02 μg/kg, i.v. bolus) caused an acute increase in airways responsiveness to histamine in anaesthetized guinea-pigs prepared for recording airways resistance (R L ) and dynamic compliance (C dyn ). Aspirin pretreatment (10 mg/kg, i.v.) attenuated the return of airways responsiveness to prechallenge levels. Pretreatment with the combined cyclooxygenase/lipoxygenase inhibitors BW 755C (20 mg/kg, i.v.) and ETYA (20 mg/kg, i.v.), or with the putative cysteinyl-containing leukotriene antagonist FPL 55712 (0.25 mg/kg/min, i.v.), or a Paf antagonist SRI 63441 (2.5 mg/kg, i.v.), prevented Paf-induced increased airways responsiveness. Inhibitors of leukotriene synthesis, BW 755C and ETYA, or action, FPL 55712, had variable effects of Paf-induced bronchoconstriction. These data suggest that lipoxygenase metabolites, possibly leukotrienes, may mediate an acute increase in airways responsiveness to histamine after Paf exposure.

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  1. Department of Pharmacology, University of Melbourne, 3052, Parkville, Victoria, Australia

    G. P. Anderson & M. R. Fennessy

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Anderson, G.P., Fennessy, M.R. Lipoxygenase metabolites mediate increased airways resonsiveness to histamine after acute platelet activating factor exposure in the guinea-pig. Agents and Actions 24, 8–19 (1988). https://doi.org/10.1007/BF01968074

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