Effects of leukotriene B4 receptor antagonist, LY293111Na, on antigen-induced bronchial hyperresponsiveness and leukocyte infiltration in sensitized guinea pigs.
OBJECTIVE
LY29311 Na, 2-[2-propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxyphenoxy] propoxy] -phenoxy]-benzoic acid sodium salt, is a novel leukotriene B4 (LTB4) receptor antagonist. Its effects on guinea pig models of asthma were compared with those of dexamethasone.


METHODS
Effects of LY293111Na were tested in antigen (ovalbumin, OA)-induced bronchial hyperresponsiveness (BHR) and leukocyte accumulation in actively sensitized guinea pigs. Its effects on antigen-induced acute bronchoconstriction in passively sensitized guinea pigs were also studied.


RESULTS
LY293111 Na (10 to 30 mg/kg p.o., 1 h before and 6 h after OA challenge) inhibited BHR to acetylcholine. LY293111 Na (3 mg/kg p. o.) significantly inhibited accumulation of neutrophils in bronchoalveolar lavage (BAL) fluid 24 h after antigen challenge but it did not inhibit accumulation of eosinophils and macrophages at any doses used. In contrast, dexamethasone (30 mg/kg p.o., 4 h before OA challenge) not only inhibited BHR but also reduced the infiltration of all three types of leukocytes. A significant increase of LTB4 levels in BAL fluid was noted at 3 and 15 min after the antigen challenge. LY293111Na did not inhibit antigen-induced acute bronchoconstriction in passively sensitized guinea pigs.


CONCLUSIONS
These results indicate that LTB4 may participate in antigen-induced BHR but not in eosinophil infiltration and acute bronchoconstriction in guinea pigs.
Asanuma
F
F
Discovery Research Laboratories, Shionogi & Co, Ltd, Toyonaka, Osaka, Japan.
Kuwabara
K
K
Arimura
A
A
Furue
Y
Y
Fleisch
J H
JH
Hori
Y
Y
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000517:prevention & control*; D016084:Bronchoconstriction / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D006168:Guinea Pigs; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000032:analysis; D008297:Male; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors*
D001565:Benzoates; C094099:LY 293111; D020024:Leukotriene Antagonists; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4; D003907:Dexamethasone; D000109:Acetylcholine