Amira Pharmaceuticals, 9535 Waples St., Ste. 100 San Diego, CA 92121, USA.
Eur J Pharmacol. 2010 Jul 25;638(1-3):142-9. doi: 10.1016/j.ejphar.2010.04.031. Epub 2010 May 4.
Prostaglandin D(2) (PGD(2)) is derived from arachidonic acid and binds with high affinity to the G protein coupled receptors prostanoid DP(1) and DP(2). Interaction with DP(2) results in cell chemotaxis, eosinophil degranulation, eosinophil shape change, adhesion molecule upregulation and Th2 cytokine production. In allergic rhinitis and allergic asthma PGD(2) is released from mast cells in response to allergen challenge and may trigger symptoms such as sneezing, rhinorrhea, pruritus, mucus hypersecretion and pulmonary inflammation. In Japan, ramatroban, a dual prostanoid DP(2)/prostanoid TP receptor antagonist, is marketed for allergic rhinitis while selective DP(2) antagonists are currently under investigation as therapeutics for asthma and allergic rhinitis. In the studies described herein, we investigated the efficacy of AM156, a novel selective prostanoid DP(2) receptor antagonist, in murine models of allergic rhinitis and asthma. AM156 inhibited sneezing and nasal rubs in a model of allergic rhinitis. AM156 inhibited pulmonary inflammation and mucus hypersecretion induced by chronic inhalation of house dust mite. These results suggest that selective prostanoid DP(2) receptor antagonists such as AM156 may provide beneficial effects for the clinical treatment of diseases such as allergic rhinitis and asthma.
前列腺素 D(2)(PGD(2))源自花生四烯酸，与 G 蛋白偶联受体前列腺素 DP(1)和 DP(2)具有高亲和力结合。与 DP(2)相互作用导致细胞趋化、嗜酸性粒细胞脱颗粒、嗜酸性粒细胞形态改变、粘附分子上调和 Th2 细胞因子产生。在过敏性鼻炎和过敏性哮喘中，PGD(2)从肥大细胞中释放出来，以应对过敏原的挑战，可能引发打喷嚏、流鼻涕、瘙痒、黏液分泌过多和肺部炎症等症状。在日本，拉曲米通是一种双重前列腺素 DP(2)/前列腺素 TP 受体拮抗剂，用于治疗过敏性鼻炎，而选择性 DP(2)拮抗剂目前正在作为哮喘和过敏性鼻炎的治疗方法进行研究。在本文所述的研究中，我们研究了新型选择性前列腺素 DP(2)受体拮抗剂 AM156 在过敏性鼻炎和哮喘的小鼠模型中的疗效。AM156 抑制了过敏性鼻炎模型中的打喷嚏和鼻擦。AM156 抑制了慢性吸入屋尘螨引起的肺部炎症和黏液分泌过多。这些结果表明，选择性前列腺素 DP(2)受体拮抗剂，如 AM156，可能为过敏性鼻炎和哮喘等疾病的临床治疗提供有益效果。
