Lipoxygenase metabolites mediate increased airways responsiveness to histamine after acute platelet activating factor exposure in the guinea-pig.
Platelet activating factor (Paf, 0.02 micrograms/kg, i.v. bolus) caused an acute increase in airways responsiveness to histamine in anaesthetized guinea-pigs prepared for recording airways resistance (RL) and dynamic compliance (Cdyn). 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 on Paf-induced bronchoconstriction. These data suggest that lipoxygenase metabolites, possibly leukotrienes, may mediate an acute increase in airways responsiveness to histamine after Paf exposure.
Anderson
G P
GP
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Fennessy
M R
MR
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D002867:Chromones / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000502:physiology; D008084:Lipoxygenase / Q000378:metabolism*; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D011806:Quinolinium Compounds / Q000494:pharmacology; D013189:SRS-A / Q000502:physiology
D002867:Chromones; D010972:Platelet Activating Factor; D011720:Pyrazoles; D011806:Quinolinium Compounds; D013189:SRS-A; C050531:SRI 63-441; D015117:5,8,11,14-Eicosatetraynoic Acid; D007975:Leukotriene B4; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D006632:Histamine; C006312:FPL 55712; D008084:Lipoxygenase; D001241:Aspirin