Antagonism of antigen-induced contraction of isolated guinea-pig trachea by 5-lipoxygenase inhibitors.
Tracheal strips were obtained from guinea pigs actively sensitized to chicken ovalbumin (OA). OA-induced contractile responses, obtained by cumulative log addition, were found to be comparable both temporally and in magnitude with responses obtained by single addition of OA. The concentration-response curve obtained by cumulative addition of OA was partially inhibited by pretreatment of tissues with chlorpheniramine. On tracheal spirals treated with chlorpheniramine, indomethacin enhanced OA-induced contractile responses. In the presence of chlorpheniramine and indomethacin, pretreatment with one of the reference 5-lipoxygenase inhibitors (ETYA, NDGA, phenidone or BW-755C) both reduced the maximum contractile response and produced a rightward shift of the OA concentration-response curve. The data suggest that cumulative log addition of OA, on the indomethacin- and chlorpheniramine-treated guinea-pig trachea, is a useful model for evaluating compounds active as either inhibitors of 5-lipoxygenase or antagonists of the products of this pathway.
Hand
J M
JM
Schwalm
S F
SF
Lewis
A J
AJ
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D001091:Arachidonate Lipoxygenases; D002396:Catechols / Q000494:pharmacology; D002744:Chlorpheniramine / Q000494:pharmacology; D006168:Guinea Pigs; D006967:Hypersensitivity / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors; D008297:Male; D009637:Masoprocol; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000503:physiopathology; D011720:Pyrazoles / Q000494:pharmacology; D013189:SRS-A / Q000037:antagonists & inhibitors*; D014132:Trachea / Q000276:immunology / Q000503:physiopathology*
D002396:Catechols; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D013189:SRS-A; D015117:5,8,11,14-Eicosatetraynoic Acid; D002744:Chlorpheniramine; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D009637:Masoprocol; D001091:Arachidonate Lipoxygenases; C015429:phenidone; D007213:Indomethacin