Involvement of cysteinyl leukotrienes in biphasic increase of nasal airway resistance of antigen-induced rhinitis in guinea pigs.
We examined the effect of a specific cysteinyl leukotriene (LT) receptor antagonist, 4-oxo-8-[4-(4-phenylbutoxy)benzoylamino]-2-(tetrazol-5-yl)-4 H-1-benzopyran hemihydrate (pranlukast), on a novel model of allergic rhinitis induced by repeated intranasal ovalbumin challenge in actively sensitized guinea pigs. Repeated intranasal ovalbumin challenge caused a biphasic increase of nasal airway resistance, peaking 0.5 and 4 h after the final challenge. The early-phase response was accompanied by an increase in sneezing and nasal secretion, while that in the late phase was associated with edema and eosinophil infiltration of the nasal mucosa. Analysis of nasal lavage fluid showed that cysteinyl LTs increased in both phases. Pranlukast, when administered 1 h before every ovalbumin challenge, dose-dependently suppressed the increase of nasal airway resistance in the early- and late phase with evidence of histopathological improvements in the late phase. Pranlukast, however, failed to suppress sneezing and nasal secretion. We suggest that cysteinyl LTs play an important role in allergic rhinitis especially in the nasal obstruction due to edema of the nasal mucosa membrane.
Fujita
M
M
Minase Research Institute, Ono Pharmaceutical, Mishima, Osaka, Japan.
Yonetomi
Y
Y
Shimouchi
K
K
Takeda
H
H
Aze
Y
Y
Kawabata
K
K
Ohno
H
H
D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D002867:Chromones / Q000627:therapeutic use*; D003545:Cysteine / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000502:physiology; D004195:Disease Models, Animal; D006168:Guinea Pigs; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D015289:Leukotrienes / Q000302:isolation & purification / Q000502:physiology; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism / Q000473:pathology; D010047:Ovalbumin; D012221:Rhinitis, Allergic, Perennial / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D015842:Serine Proteinase Inhibitors / Q000009:adverse effects
D002867:Chromones; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D015842:Serine Proteinase Inhibitors; C112381:cysteinyl-leukotriene; D010047:Ovalbumin; D003545:Cysteine; C047681:pranlukast