関: MT2 melatonin receptor

WordNet

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
the 13th letter of the Roman alphabet (同)m

PrepTutorEJDIC

=sense organ / 受信装置
Mach number / mark[s] / Monsieur
Montana

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/01/28 01:07:17」(JST)

wiki en

Melatonin receptor 1B, also known as MTNR1B, is a protein that in humans is encoded by the MTNR1B gene.^[1]^[2]

Function

This gene encodes the MT₂ protein, one of two high-affinity forms of a receptor for melatonin, the primary hormone secreted by the pineal gland. This gene product is an integral membrane protein that is a G-protein coupled, 7-transmembrane receptor. It is found primarily in the retina and brain; however, this detection requires RT-PCR. It is thought to participate in light-dependent functions in the retina and may be involved in the neurobiological effects of melatonin.^[1]

Clinical significance

Several studies have identified MTNR1B receptor mutations that are associated with increased average blood sugar level and around a 20 percent elevated risk of developing type 2 diabetes.^[3]^[4]^[5] MTNR1B mRNA is expressed in human islets, and immunocytochemistry confirms that it is primarily localized in beta cells in islets.^[4]

MT2R Ligands

The following MT2R ligands have selectivity over MT1R:

Compound 3d: antagonist with sub-nM affinity^[6]
Compound 18f: antagonist and compound 18g partial agonist: sub-nM affinity, >100-fold selectivity over MT1^[7]
Compound 14: antagonist^[8]
Compound 13: agonist^[9]

References

^ ^a ^b "Entrez Gene: MTNR1B melatonin receptor 1B".
^ Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF (September 1995). "Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor". Proc. Natl. Acad. Sci. U.S.A. 92 (19): 8734–8. doi:10.1073/pnas.92.19.8734. PMC 41041. PMID 7568007.
^ "Gene That Regulates Glucose Levels And Increases Risk For Diabetes Identified". ScienceDaily. 2008-06-28. Retrieved 2009-01-18. ; "Body Clock Linked To Diabetes And High Blood Sugar In New Genome-wide Study". ScienceDaily. 2008-12-08. Retrieved 2009-01-18. ; "Is There A Relationship Between Sleep-wake Rhythm And Diabetes? A New Gene Variant Influences Fasting Glucose Levels Via The Melatonin Metabolism". ScienceDaily. 2009-01-16. Retrieved 2009-01-18.
^ ^a ^b Prokopenko I, Langenberg C, Florez JC, et al. (January 2009). "Variants in MTNR1B influence fasting glucose levels". Nat. Genet. 41 (1): 77–81. doi:10.1038/ng.290. PMC 2682768. PMID 19060907. ; Lyssenko V, Nagorny CL, Erdos MR, et al. (January 2009). "Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion". Nat. Genet. 41 (1): 82–8. doi:10.1038/ng.288. PMID 19060908. ; Bouatia-Naji N, Bonnefond A, Cavalcanti-Proença C, et al. (January 2009). "A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk". Nat. Genet. 41 (1): 89–94. doi:10.1038/ng.277. PMID 19060909.
^ Staiger H, Machicao F, Schäfer SA, et al. (2008). Maedler, Kathrin, ed. "Polymorphisms within the novel type 2 diabetes risk locus MTNR1B determine beta-cell function". PLoS ONE 3 (12): e3962. doi:10.1371/journal.pone.0003962. PMC 2597741. PMID 19088850.
^ Rivara S, Lodola A, Mor M, et al. (2007). "N-(substituted-anilinoethyl)amides: design, synthesis, and pharmacological characterization of a new class of melatonin receptor ligands". J. Med. Chem. 50 (26): 6618–26. doi:10.1021/jm700957j. PMID 18052314.
^ Bedini A, Spadoni G, Gatti G, et al. (2006). "Design and synthesis of N-(3,3-diphenylpropenyl)alkanamides as a novel class of high-affinity MT2-selective melatonin receptor ligands". J. Med. Chem. 49 (25): 7393–403. doi:10.1021/jm060850a. PMID 17149869.
^ Yous S, Durieux-Poissonnier S, Lipka-Belloli E, et al. (2003). "Design and synthesis of 3-phenyl tetrahydronaphthalenic derivatives as new selective MT2 melatoninergic ligands". Bioorg. Med. Chem. 11 (5): 753–9. doi:10.1016/S0968-0896(02)00473-X. PMID 12538005.
^ Mattson RJ, Catt JD, Keavy D, et al. (2003). "Indanyl piperazines as melatonergic MT2 selective agents". Bioorg. Med. Chem. Lett. 13 (6): 1199–202. doi:10.1016/S0960-894X(03)00090-8. PMID 12643943.

External links

"Melatonin Receptors: MT₂". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. インスリン受容体の構造および機能 structure and function of the insulin receptor
2. 免疫不全症を引き起こすCD3／T細胞受容体複合体疾患 cd3 t cell receptor complex disorders causing immunodeficiency
3. T細胞受容体の遺伝学 t cell receptor genetics
4. T細胞受容体シグナル伝達 t cell receptor signaling
5. メラトニンの生理学および臨床使用 physiology and clinical use of melatonin

English Journal

Chronic agomelatine treatment corrects behavioral, cellular, and biochemical abnormalities induced by prenatal stress in rats.

Morley-Fletcher S, Mairesse J, Soumier A, Banasr M, Fagioli F, Gabriel C, Mocaer E, Daszuta A, McEwen B, Nicoletti F, Maccari S.SourceNeuroplasticity Team, UMR 8576 CNRS Structural and Functional Glycobiology Unit, University Lille North of France (USTL), 59655, Villeneuve d'Ascq, France.
Psychopharmacology.Psychopharmacology (Berl).2011 Oct;217(3):301-13. Epub 2011 Apr 19.
RATIONALE AND OBJECTIVES: The rat model of prenatal restraint stress (PRS) replicates factors that are implicated in the etiology of anxious/depressive disorders. We used this model to test the therapeutic efficacy of agomelatine, a novel antidepressant that behaves as a mixed MT1/MT2 melatonin rece
PMID 21503609

Membrane-type Matrix Metalloproteinase-3 Regulates Neuronal Responsiveness to Myelin through Nogo-66 Receptor 1 Cleavage.

Ferraro GB, Morrison CJ, Overall CM, Strittmatter SM, Fournier AE.SourceFrom the Department of Neurology and Neurosurgery, Montreal Neurological Institute, Montreal, Quebec H3A 2B4, Canada.
The Journal of biological chemistry.J Biol Chem.2011 Sep 9;286(36):31418-24. Epub 2011 Jul 18.
Nogo-66 receptor 1 (NgR1) is a glycosylphosphatidylinositol-anchored receptor for myelin-associated inhibitors that restricts plasticity and axonal regrowth in the CNS. NgR1 is cleaved from the cell surface of SH-SY5Y neuroblastoma cells in a metalloproteinase-dependent manner; however, the mechanis
PMID 21768085

Japanese Journal

メラトニン受容体作動薬ラメルテオン(ロゼレム^【○!R】錠8mg)の薬理作用と臨床試験成績

平井圭介,加藤浩紀,西川久夫,行弘信仁,西山啓次,宮本政臣
日本薬理学雑誌 136(1), 51-60, 2010-07-01
… 弛緩作用，前向性健忘，反跳性不眠，依存性などの種々の有害作用を惹起する．これに対してラメルテオン（Ramelteon，TAK-375，商品名Rozerem®）は，主に視床下部視交叉上核に存在するメラトニン受容体（MT1/MT2受容体）にアゴニストとして作用してcAMP産生系を抑制し，サルおよびネコで強力な睡眠誘発作用を示した．その睡眠パターンは自然睡眠に極めて近いものであった．また，既存薬で見られる学習記憶障害，運 …
NAID 10026544589

Acute effects of melatonin and its time of administration on core body temperature and heart rate in cynomolgus monkeys

INUI Yoshitaka,HAZEKI Osamu
Journal of toxicological sciences 35(3), 383-391, 2010-06-01
… Any effects on the CBT and HR from melatonin administration were not inhibited by luzindole, an MT1/MT2 receptor antagonist, whereas N-acetyl-5-hydroxytryptamine, a ligand of the MT3 binding site, mimicked all the actions of melatonin. …
NAID 10026469845

「MT2 melatonin receptor」

Melatonin receptor 1B
Identifiers
Symbols	MTNR1B ; FGQTL2; MEL-1B-R; MT2
External IDs	OMIM: 600804 MGI: 2181726 HomoloGene: 4350 IUPHAR: MT2 ChEMBL: 1946 GeneCards: MTNR1B Gene
Gene ontology
Molecular function	• G-protein coupled receptor activity; • protein binding; • melatonin receptor activity;
Cellular component	• plasma membrane; • integral component of plasma membrane;
Biological process	• G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; • synaptic transmission; • glucose homeostasis; • regulation of insulin secretion;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;