Synergism between cysteinyl leukotrienes and thromboxane A2 to induce allergic late phase nasal blockage in guinea pigs.
We examined whether cysteinyl leukotrienes (CysLTs) and thromboxane (TX) A2 are synergistically involved in a cedar pollen-induced allergic late phase nasal blockage in guinea pigs. Sensitized animals were repeatedly challenged by pollen inhalation once every week. Combined treatment with pranlukast (a CysLT antagonist) and seratrodast (a TXA2 antagonist) inhibited late phase nasal blockage, but the magnitude of inhibition (approximately 50%) was equal to those of the respective single treatments, suggesting that CysLTs produced late after challenge induces TXA2 production in the nasal tissue, as in the case of the lung of this species. However, pranlukast did not affect TXB2 increase in the nasal tissue. In contrast, combined intranasal instillation of LTD4 and U-46619 (a TXA2 mimetic) produced much greater nasal blockage than single administration of each agonist in sensitized animals. Therefore, allergic late phase nasal blockage should be induced by synergistic activity of CysLTs and TXA2 at the effector organ.
Nakanishi
Yasutomo
Y
Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
Nabe
Takeshi
T
Mizutani
Nobuaki
N
Takenaka
Hiroshi
H
Kohno
Shigekatsu
S
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000008:administration & dosage; D000818:Animals; D016227:Benzoquinones / Q000008:administration & dosage; D002867:Chromones / Q000008:administration & dosage; D006168:Guinea Pigs; D006538:Heptanoic Acids / Q000008:administration & dosage; D006967:Hypersensitivity / Q000503:physiopathology*; D017998:Leukotriene D4 / Q000008:administration & dosage; D015289:Leukotrienes / Q000502:physiology*; D008297:Male; D009296:Nasal Cavity / Q000503:physiopathology; D013928:Thromboxane A2 / Q000096:biosynthesis / Q000502:physiology*
D016227:Benzoquinones; D002867:Chromones; D006538:Heptanoic Acids; D015289:Leukotrienes; C060230:seratrodast; D013928:Thromboxane A2; D017998:Leukotriene D4; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C047681:pranlukast