Pettipher Roy, Hansel Trevor T, Armer Richard
Oxagen Limited, 91 Milton Park, Abingdon, Oxfordshire OX14 4RY, UK.
Nat Rev Drug Discov. 2007 Apr;6(4):313-25. doi: 10.1038/nrd2266.
Immunological activation of mast cells is an important trigger in the cascade of inflammatory events leading to the manifestation of allergic diseases. Pharmacological studies using the recently discovered DP(1) and CRTH2 antagonists combined with genetic analysis support the view that these receptors have a pivotal role in mediating aspects of allergic diseases that are resistant to current therapy. This Review focuses on the emerging roles that DP(1) and CRTH2 (also known as DP(2)) have in acute and chronic aspects of allergic diseases and proposes that, rather than having opposing actions, these receptors have complementary roles in the initiation and maintenance of the allergy state. We also discuss recent progress in the discovery and development of selective antagonists of these receptors.
肥大细胞的免疫激活是导致过敏性疾病表现的炎症事件级联反应中的一个重要触发因素。使用最近发现的DP(1)和CRTH2拮抗剂并结合基因分析的药理学研究支持这样一种观点,即这些受体在介导对当前治疗有抗性的过敏性疾病方面起着关键作用。本综述重点关注DP(1)和CRTH2(也称为DP(2))在过敏性疾病急性和慢性方面所起的新作用,并提出这些受体并非具有相反作用,而是在过敏状态的启动和维持中具有互补作用。我们还讨论了这些受体选择性拮抗剂发现和开发方面的最新进展。