Inhibitory effect of a TP-receptor antagonist, S-1452, on antigen-induced nasal plasma exudation in guinea pig model for allergic rhinitis.
S-1452, a selective thromboxane (Tx) A(2) receptor (TP-receptor) antagonist, was evaluated in antigen- and U-46619 (a TxA(2) mimetic)-induced guinea pig nasal plasma exudation models. Exposure of the nasal cavity of actively sensitized guinea pigs to aerosolized ovalbumin (OA) caused marked exudation of dye into both the nasal mucosa and nasal airway lumen. These responses were significantly inhibited by S-1452 (30 mg/kg, p.o.) as well as an H(1)-antihistamine, diphenhydramine (5 mg/kg, i.v.). In addition, exposure of the nasal cavity of nonsensitized guinea pigs to aerosolized U-46619 or histamine also resulted in nasal plasma exudation, and S-1452 (1 mg/kg, p.o.) almost completely suppressed the U-46619-induced response but did not affect the histamine-induced one, even at a high dose of 30 mg/kg. These results indicate that TxA(2) as well as histamine may play an important role in antigen-induced nasal plasma exudation in guinea pigs, and S-1452 can be expected to be useful for the treatment of allergic rhinitis.
Yasui
K
K
Discovery Research Laboratories, Shionogi & Co., Ltd, Toyonaka, Osaka, Japan.
Asanuma
F
F
Arimura
A
A
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000009:adverse effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D004195:Disease Models, Animal; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D017817:Nasal Lavage Fluid / Q000276:immunology; D009297:Nasal Mucosa / Q000187:drug effects* / Q000276:immunology; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors* / Q000276:immunology; D012221:Rhinitis, Allergic, Perennial / Q000139:chemically induced; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000941:Antigens; D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D011448:Prostaglandin Antagonists; D017482:Receptors, Thromboxane; D014662:Vasoconstrictor Agents; C056566:S 145; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid