부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ejphar.2007.09.014 Byline: Kiyoshi Yasui (a), Fujio Asanuma (a), Yosuke Hirano (a), Michitaka Shichijo (a), Masashi Deguchi (a), Akinori Arimura (b) Keywords: PGD.sub.2; Prostanoid DP receptor; Allergic rhinitis; Nasal blockage; Nasal hyperresponsiveness; S-5751; Histamine; TXA.sub.2; U46619 Abstract: We examined the role of prostanoid DP receptor in nasal blockage in an experimental allergic rhinitis model in guinea pigs. Local inhalation of prostaglandin D.sub.2 (PGD.sub.2) to the nasal cavity resulted in an increase in intranasal pressure in guinea pigs actively sensitized by repeated antigen exposure but not in non-sensitized guinea pigs. Nasal hyperresponsiveness was observed when the guinea pigs were exposed to histamine and U-46619 (11[alpha], 9[alpha]-epoxymethano-PGH.sub.2; a thromboxane (TX) A.sub.2 mimetic) after repeated antigen exposure. S-5751 ((Z)-7-[(1R,2R,3S,5S)-2-(5-hydroxybenzo[b]thiophen-3-ylcarbonylamino)-10-norpinan-3-yl]hept-5-enoic acid), a prostanoid DP receptor antagonist, inhibited not only PGD.sub.2-induced nasal blockage but also nasal hyperresponsiveness to histamine and U-46619 in sensitized guinea pigs. Combined exposure of the nasal cavity of guinea pigs to an aerosol of PGD.sub.2 with histamine or U-46619 at sub-threshold concentrations synergistically caused a marked increase in intranasal pressure. These responses were significantly suppressed by S-5751. These results suggest that PGD.sub.2 plays a critical role in the increase in intranasal pressure via prostanoid DP receptor, probably through synergistically enhancing the nasal response with other chemical mediators released from mast cells and other inflammatory cells activated by allergens. Author Affiliation: (a) Frontier Drug Discovery, Discovery Research Laboratories, Shionogi & Co., Ltd., 1-1, Futaba-cho 3-chome, Toyonaka, Osaka 561-0825, Japan (b) Strategic Development Department, Shionogi & Co., Ltd., 12-4, Sagisu 5-chome, Fukushima-ku, Osaka 553-0002, Japan Article History: Received 14 May 2007; Revised 5 September 2007; Accepted 18 September 2007