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deprive of parents
a young animal without a mother
a child who has lost both parents
someone or something who lacks support or care or supervision
the first line of a paragraph that is set as the last line of a page or column
a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response
deprived of parents by death or desertion

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『孤児』 / 孤児の / …‘を'孤児にする
=sense organ / 受信装置

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/09/22 05:53:01」(JST)

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An orphan receptor is an apparent receptor that has a similar structure to other identified receptors but whose endogenous ligand has not yet been identified. If a ligand for an orphan receptor is later discovered, the receptor is referred to as an "adopted orphan"^{[citation needed]}.

Examples

Examples of orphan receptors are found in the G protein-coupled receptor (GPCR)^[1]^[2]^[3] and nuclear receptor^[4]^[5]^[6] families. GPCR orphan receptors are usually given the name "GPR" followed by a number, for example GPR1.

If an endogenous ligand is found, the orphan receptor is "adopted". An example is the receptor FXR, which is activated by bile acids.^[7] Adopted orphan receptors in the nuclear receptor group include the farnesoid X receptor (FXR), liver X receptor (LXR), and peroxisome proliferator-activated receptor (PPAR). Another example of an orphan receptor site is the PCP binding site in the NMDA receptor,^[8] a type of ligand-gated ion channel. This is where the recreational drug PCP works, but no endogenous ligand is known for this site.

Discovery

Historically, receptors were discovered by using ligands to "fish" for their receptors. Hence by definition, these receptors were not orphans. However, with modern molecular biology techniques such as screening of cDNA libraries, it becomes possible to identify related receptors based on sequence similarity to known receptors without knowing what their ligands are.

References

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

External links

"Class A Orphans GPCRs". IUPHAR Database. International Union of Pharmacology.
"Class B Orphans GPCRs". IUPHAR Database. International Union of Pharmacology.
"Class C Orphans GPCRs". IUPHAR Database. International Union of Pharmacology.

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English Journal

The emerging pharmacology and function of GPR35 in the nervous system.

Mackenzie AE1, Milligan G2.
Neuropharmacology.Neuropharmacology.2017 Feb;113(Pt B):661-671. doi: 10.1016/j.neuropharm.2015.07.035. Epub 2015 Jul 29.
G protein-coupled receptor 35 (GPR35) is an orphan G protein-coupled receptor (GPCR) that can be activated by kynurenic acid at high micromolar concentrations. A previously unappreciated mechanism of action of GPR35 has emerged as a Gαi/o-coupled inhibitor of synaptic transmission, a finding that h
PMID 26232640

In vivo and in silico studies to identify mechanisms associated with Nurr1 modulation following early life exposure to permethrin in rats.

Fedeli D1, Montani M2, Bordoni L3, Galeazzi R4, Nasuti C1, Correia-Sá L5, Domingues VF5, Jayant M6, Brahmachari V6, Massaccesi L4, Laudadio E4, Gabbianelli R7.
Neuroscience.Neuroscience.2017 Jan 6;340:411-423. doi: 10.1016/j.neuroscience.2016.10.071. Epub 2016 Nov 5.
The present work was designed to study the mechanisms associated with Nurr1 modulation following early life permethrin (PERM) treatment during rat's life span. Here we demonstrate that PERM exposure in rats, at a dose close to No Observed Adverse Effect Level (NOAEL) for 15days during neonatal brain
PMID 27826104

RORγt inhibitors as potential back-ups for the phase II candidate VTP-43742 from Vitae Pharmaceuticals: patent evaluation of WO2016061160 and US20160122345.

Gege C1.
Expert opinion on therapeutic patents.Expert Opin Ther Pat.2017 Jan;27(1):1-8. Epub 2016 Nov 25.
Retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt or RORc2) is a key transcription factor for the differentiation of naïve proinflammatory CD4+ T cells and the production of T helper-17 (TH17) cells. Inhibiting RORγt activity is thought to be beneficial in targeting a variety
PMID 27852111

Japanese Journal

Gpr176 is a Gz-linked orphan G-protein-coupled receptor that sets the pace of circadian behaviour.

Nature communications 7, 2016-02-17
NAID 120005705946

Promoter hypomethylation of RAR-related orphan receptor α 1 is correlated with unfavorable clinicopathological features in patients with colorectal cancer