Clinical Pharmacology Unit, University of Cambridge, Level 6, Centre for Clinical Investigation, Box 110, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Pharmacol Rev. 2013 May 17;65(3):967-86. doi: 10.1124/pr.112.007179. Print 2013 Jul.
In 2005, the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) published a catalog of all of the human gene sequences known or predicted to encode G protein-coupled receptors (GPCRs), excluding sensory receptors. This review updates the list of orphan GPCRs and describes the criteria used by NC-IUPHAR to recommend the pairing of an orphan receptor with its cognate ligand(s). The following recommendations are made for new receptor names based on 11 pairings for class A GPCRs: hydroxycarboxylic acid receptors [HCA₁ (GPR81) with lactate, HCA₂ (GPR109A) with 3-hydroxybutyric acid, HCA₃ (GPR109B) with 3-hydroxyoctanoic acid]; lysophosphatidic acid receptors [LPA₄ (GPR23), LPA₅ (GPR92), LPA₆ (P2Y5)]; free fatty acid receptors [FFA4 (GPR120) with omega-3 fatty acids]; chemerin receptor (CMKLR1; ChemR23) with chemerin; CXCR7 (CMKOR1) with chemokines CXCL12 (SDF-1) and CXCL11 (ITAC); succinate receptor (SUCNR1) with succinate; and oxoglutarate receptor [OXGR1 with 2-oxoglutarate]. Pairings are highlighted for an additional 30 receptors in class A where further input is needed from the scientific community to validate these findings. Fifty-seven human class A receptors (excluding pseudogenes) are still considered orphans; information has been provided where there is a significant phenotype in genetically modified animals. In class B, six pairings have been reported by a single publication, with 28 (excluding pseudogenes) still classified as orphans. Seven orphan receptors remain in class C, with one pairing described by a single paper. The objective is to stimulate research into confirming pairings of orphan receptors where there is currently limited information and to identify cognate ligands for the remaining GPCRs. Further information can be found on the IUPHAR Database website (http://www.iuphar-db.org).
2005 年，国际基础和临床药理学联合会受体命名和药物分类委员会（NC-IUPHAR）发布了一份目录，列出了所有已知或预测编码 G 蛋白偶联受体（GPCR）的人类基因序列，不包括感觉受体。本综述更新了孤儿 GPCR 列表，并描述了 NC-IUPHAR 用于推荐孤儿受体与其同源配体配对的标准。根据 A 类 GPCR 的 11 对配对，提出了新受体名称的以下建议：羟羧酸受体[HCA₁（GPR81）与乳酸，HCA₂（GPR109A）与 3-羟基丁酸，HCA₃（GPR109B）与 3-羟基辛酸]；溶血磷脂酸受体[LPA₄（GPR23），LPA₅（GPR92），LPA₆（P2Y5）]；游离脂肪酸受体[FFA4（GPR120）与 ω-3 脂肪酸]；趋化素受体（CMKLR1；ChemR23）与趋化素；CXCR7（CMKOR1）与趋化因子 CXCL12（SDF-1）和 CXCL11（ITAC）；琥珀酸受体（SUCNR1）与琥珀酸；以及氧化戊二酸受体[OXGR1 与 2-氧戊二酸]。在 A 类中，另外 30 个受体的配对得到了强调，需要科学界提供进一步的信息来验证这些发现。57 个人类 A 类受体（不包括假基因）仍被认为是孤儿；在基因修饰动物中存在显著表型的情况下，提供了相关信息。在 B 类中，有一篇文献报道了 6 对配对，28 个（不包括假基因）仍被归类为孤儿。C 类仍有 7 个孤儿受体，其中一个配对仅由一篇论文描述。目的是刺激对目前信息有限的孤儿受体配对的研究，并确定其余 GPCR 的同源配体。更多信息可在 IUPHAR 数据库网站（http://www.iuphar-db.org）上找到。
