Sugahara Shingo, Nabe Takeshi, Mizutani Nobuaki, Takenaka Hiroshi, Kohno Shigekatsu
Department of Pharmacology, Kyoto Pharmaceutical University, 5 Nakauchi, Misasagi, Yamashina, Kyoto 607-8414, Japan.
Eur J Pharmacol. 2003 Aug 29;476(3):229-37. doi: 10.1016/s0014-2999(03)02185-x.
We evaluated roles of kinins in allergen-induced nasal blockage and sneezing, and development of nasal hyperresponsiveness to leukotriene D4 in a Japanese cedar pollen-induced allergic rhinitis model of guinea pigs. Sensitised guinea pigs were repeatedly challenged by pollen inhalation once every week. Neither a bradykinin B1 receptor antagonist, des-Arg9-[Leu8]bradykinin nor a bradykinin B2 receptor antagonist, icatibant suppressed allergen-induced sneezing and nasal blockage. However, development of nasal hyperresponsiveness to leukotriene D4 was significantly suppressed by them. The amount of bradykinin in nasal cavity lavage fluid was immediately increased after the challenge. In non-sensitised animals, hyperresponsiveness to leukotriene D4 was developed by a bradykinin B2 receptor agonist, bradykinin, but not by a bradykinin B1 receptor agonist, des-Arg10-kallidin, while in the sensitised-challenged animal, both agonists developed hyperresponsiveness. In conclusion, the nasal hyperresponsiveness appeared to be induced by kinins produced in response to the antigen challenge through activation of not only bradykinin B2 but also B1 receptors.
我们在豚鼠日本雪松花粉诱导的变应性鼻炎模型中评估了激肽在变应原诱导的鼻阻塞和喷嚏中的作用,以及鼻对白三烯D4高反应性的发展。致敏豚鼠每周吸入一次花粉进行反复激发。缓激肽B1受体拮抗剂去-Arg9-[Leu8]缓激肽和缓激肽B2受体拮抗剂依替巴肽均不能抑制变应原诱导的喷嚏和鼻阻塞。然而,它们能显著抑制鼻对白三烯D4高反应性的发展。激发后鼻腔灌洗液中缓激肽的量立即增加。在未致敏动物中,缓激肽B2受体激动剂缓激肽可使鼻对白三烯D4产生高反应性,而缓激肽B1受体激动剂去-Arg10-胰激肽则不能,而在致敏激发动物中,两种激动剂均可使鼻产生高反应性。总之,鼻高反应性似乎是由抗原激发后通过激活缓激肽B2和B1受体产生的激肽诱导的。