Dept. of Biological Sciences RD3-2B, Allergan, Inc., 2525 Dupont Dr., Irvine, CA 92612, USA.
Pharmacol Rev. 2011 Sep;63(3):471-538. doi: 10.1124/pr.110.003517. Epub 2011 Jul 13.
It is now more than 15 years since the molecular structures of the major prostanoid receptors were elucidated. Since then, substantial progress has been achieved with respect to distribution and function, signal transduction mechanisms, and the design of agonists and antagonists (http://www.iuphar-db.org/DATABASE/FamilyIntroductionForward?familyId=58). This review systematically details these advances. More recent developments in prostanoid receptor research are included. The DP(2) receptor, also termed CRTH2, has little structural resemblance to DP(1) and other receptors described in the original prostanoid receptor classification. DP(2) receptors are more closely related to chemoattractant receptors. Prostanoid receptors have also been found to heterodimerize with other prostanoid receptor subtypes and nonprostanoids. This may extend signal transduction pathways and create new ligand recognition sites: prostacyclin/thromboxane A(2) heterodimeric receptors for 8-epi-prostaglandin E(2), wild-type/alternative (alt4) heterodimers for the prostaglandin FP receptor for bimatoprost and the prostamides. It is anticipated that the 15 years of research progress described herein will lead to novel therapeutic entities.
自主要前列腺素受体的分子结构被阐明以来,已经过去了 15 多年。此后,在分布和功能、信号转导机制以及激动剂和拮抗剂的设计方面取得了实质性进展(http://www.iuphar-db.org/DATABASE/FamilyIntroductionForward?familyId=58)。本综述系统地详述了这些进展。还包括了前列腺素受体研究的最新进展。DP(2)受体,也称为 CRTH2,与 DP(1)和原始前列腺素受体分类中描述的其他受体在结构上几乎没有相似之处。DP(2)受体与趋化因子受体更为密切相关。还发现前列腺素受体与其他前列腺素受体亚型和非前列腺素异二聚化。这可能会扩展信号转导途径并创建新的配体识别位点:用于 8-epi-前列腺素 E(2)的前列腺素 I2/血栓素 A2 异二聚体受体、用于比马前列素的前列腺素 FP 受体的野生型/替代(alt4)异二聚体和前列腺素。预计本文所述的 15 年研究进展将导致新的治疗实体。