孤兒受體

孤兒受體 （英語：orphan receptor）是指一些與其它已確認的受體結構上明顯相似，但其內源配體還未發現的受體。一旦對應的配體被找到，該受體就被稱為「領養孤兒」（"adopted orphan"）。

例子

在G蛋白偶聯受體(GPCR)^[1]^[2]^[3]和核受體^[4]^[5]^[6]家族中有許多孤兒受體的例子。GPCR中的孤兒受體通常用"GPR" 加一個數字來命名，比如GPR1。

找到內源性配體的過程被稱為「領養孤兒」，一個例子是FXR，後來發現它的配體為膽汁酸^[7]。被領養的孤兒受體在核受體中很常見，包括類法尼醇x受體（FXR）、肝X受體（LXR）以及過氧化物酶體增殖物活化受體（PPAR）。還有一種情況，如消遣性毒品PCP可以做為NMDA受體（一種配體門控離子通道）的配體^[8]，但NMDA受體的內源性配體仍未找到。

發現

在過去，都是通過配體去尋找對應的受體，這樣找出來的受體肯定不會是孤兒受體。但隨著現代分子生物技術的發展特別是cDNA 文庫的出現，通過檢索已知受體的相似序列來尋找受體，使得發現一些還沒找到配體的受體成為了可能。

參考文獻

^ 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.

外部連結

Class A Orphans GPCRs. IUPHAR Database. International Union of Pharmacology. （原始內容存檔於2019-11-11）.
Class B Orphans GPCRs. IUPHAR Database. International Union of Pharmacology. （原始內容存檔於2019-11-01）.
Class C Orphans GPCRs. IUPHAR Database. International Union of Pharmacology. （原始內容存檔於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.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]