孤儿受体

孤儿受体 （英語：orphan receptor）是指一些与其它已确认的受体结构上明显相似，但其内源配体还未发现的受体。一旦对应的配体被找到，该受体就被称为“领养孤儿”（"adopted orphan"）。

例子

在G蛋白偶联受体(GPCR)^[1]^[2]^[3]和核受体^[4]^[5]^[6]家族中有许多孤儿受体的例子。GPCR中的孤儿受体通常用"GPR" 加一个数字来命名，比如GPR1。

找到内源性配体的过程被称为“领养孤儿”，一个例子是FXR，后来发现它的配体为胆汁酸^[7]。被领养的孤儿受体在核受体中很常见，包括类法尼醇x受体（FXR）、肝X受体（LXR）以及过氧化物酶体增殖物活化受体（PPAR）。还有一种情况，如消遣性毒品PCP可以做为NMDA受体（一种配体门控离子通道）的配体^[8]，但NMDA受体的内源性配体仍未找到。

发现

在过去，都是通过配体去寻找对应的受体，这样找出来的受体肯定不会是孤儿受体。但随着现代分子生物技术的发展特别是cDNA 文库的出现，通过检索已知受体的相似序列来寻找受体，使得发现一些还没找到配体的受体成为了可能。

参考文献

^ Levoye A, Dam J, Ayoub MA, Guillaume JL, Jockers R. Do orphan G-protein-coupled receptors have ligand-independent functions? New insights from receptor heterodimers. EMBO Rep. 2006, 7 (11): 1094–8. PMC 1679777 . PMID 17077864. doi:10.1038/sj.embor.7400838.
^ Civelli O, Saito Y, Wang Z, Nothacker HP, Reinscheid RK. Orphan GPCRs and their ligands. Pharmacol Ther. 2006, 110 (3): 525–32. PMID 16289308. doi:10.1016/j.pharmthera.2005.10.001.
^ Wise A, Jupe SC, Rees S. The identification of ligands at orphan G-protein coupled receptors. Annu Rev Pharmacol Toxicol. 2004, 44 (February): 43–66. PMID 14744238. doi:10.1146/annurev.pharmtox.44.101802.121419.
^ Giguère V. Orphan nuclear receptors: from gene to function. Endocr. Rev. October 1999, 20 (5): 689–725. PMID 10529899. doi:10.1210/er.20.5.689.
^ Benoit G, Cooney A, Giguere V, Ingraham H, Lazar M, Muscat G, Perlmann T, Renaud JP, Schwabe J, Sladek F, Tsai MJ, Laudet V. International Union of Pharmacology. LXVI. Orphan nuclear receptors. Pharmacol Rev. 2006, 58 (4): 798–836. PMID 17132856. doi:10.1124/pr.58.4.10.
^ Shi Y. Orphan Nuclear Receptors in Drug Discovery. Drug Discov. Today. June 2007, 12 (11–12): 440–5. PMC 2748783 . PMID 17532527. doi:10.1016/j.drudis.2007.04.006.
^ Mi LZ, Devarakonda S, Harp JM, Han Q, Pellicciari R, Willson TM, Khorasanizadeh S, Rastinejad F. Structural basis for bile acid binding and activation of the nuclear receptor FXR. Mol. Cell. April 2003, 11 (4): 1093–100. PMID 12718893. doi:10.1016/S1097-2765(03)00112-6.
^ Fagg GE. Phencyclidine and related drugs bind to the activated N-methyl-D-aspartate receptor-channel complex in rat brain membranes. Neurosci. Lett. May 1987, 76 (2): 221–7. PMID 2438606. doi:10.1016/0304-3940(87)90719-1.

外部链接

Class A Orphans GPCRs. IUPHAR Database. International Union of Pharmacology. （原始内容存档于2019-11-11）.
Class B Orphans GPCRs. IUPHAR Database. International Union of Pharmacology. （原始内容存档于2019-11-01）.
Class C Orphans GPCRs. IUPHAR Database. International Union of Pharmacology. （原始内容存档于2019-11-06）.

[Levoye_2006-1] Levoye A, Dam J, Ayoub MA, Guillaume JL, Jockers R. Do orphan G-protein-coupled receptors have ligand-independent functions? New insights from receptor heterodimers. EMBO Rep. 2006, 7 (11): 1094–8. PMC 1679777 . PMID 17077864. doi:10.1038/sj.embor.7400838.

[Civelli_2006-2] Civelli O, Saito Y, Wang Z, Nothacker HP, Reinscheid RK. Orphan GPCRs and their ligands. Pharmacol Ther. 2006, 110 (3): 525–32. PMID 16289308. doi:10.1016/j.pharmthera.2005.10.001.

[Wise_2004-3] Wise A, Jupe SC, Rees S. The identification of ligands at orphan G-protein coupled receptors. Annu Rev Pharmacol Toxicol. 2004, 44 (February): 43–66. PMID 14744238. doi:10.1146/annurev.pharmtox.44.101802.121419.

[pmid10529899-4] Giguère V. Orphan nuclear receptors: from gene to function. Endocr. Rev. October 1999, 20 (5): 689–725. PMID 10529899. doi:10.1210/er.20.5.689.

[Benoit_2006-5] Benoit G, Cooney A, Giguere V, Ingraham H, Lazar M, Muscat G, Perlmann T, Renaud JP, Schwabe J, Sladek F, Tsai MJ, Laudet V. International Union of Pharmacology. LXVI. Orphan nuclear receptors. Pharmacol Rev. 2006, 58 (4): 798–836. PMID 17132856. doi:10.1124/pr.58.4.10.

[pmid17532527-6] Shi Y. Orphan Nuclear Receptors in Drug Discovery. Drug Discov. Today. June 2007, 12 (11–12): 440–5. PMC 2748783 . PMID 17532527. doi:10.1016/j.drudis.2007.04.006.

[pmid12718893-7] Mi LZ, Devarakonda S, Harp JM, Han Q, Pellicciari R, Willson TM, Khorasanizadeh S, Rastinejad F. Structural basis for bile acid binding and activation of the nuclear receptor FXR. Mol. Cell. April 2003, 11 (4): 1093–100. PMID 12718893. doi:10.1016/S1097-2765(03)00112-6.

[pmid2438606-8] Fagg GE. Phencyclidine and related drugs bind to the activated N-methyl-D-aspartate receptor-channel complex in rat brain membranes. Neurosci. Lett. May 1987, 76 (2): 221–7. PMID 2438606. doi:10.1016/0304-3940(87)90719-1.

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