M4受容体、M4レセプター
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
- the imperial dynasty of China from 1368 to 1644 (同)Ming dynasty
PrepTutorEJDIC
- =sense organ / 受信装置
- Mach number / mark[s] / Monsieur
- (中国の)明,明朝(1368‐1644)
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2013/07/26 01:04:18」(JST)
[Wiki en表示]
Cholinergic receptor, muscarinic 4 |
Identifiers |
Symbols |
CHRM4; HM4; M4R |
External IDs |
OMIM: 118495 MGI: 88399 HomoloGene: 20192 IUPHAR: M4 ChEMBL: 1821 GeneCards: CHRM4 Gene |
Gene Ontology |
Molecular function |
• G-protein coupled acetylcholine receptor activity
|
Cellular component |
• plasma membrane
• integral to plasma membrane
• cell junction
• postsynaptic membrane
|
Biological process |
• signal transduction
• cell surface receptor signaling pathway
• adenylate cyclase-inhibiting G-protein coupled acetylcholine receptor signaling pathway
• G-protein coupled acetylcholine receptor signaling pathway
• cell proliferation
• response to organic substance
• regulation of acetylcholine secretion
• regulation of locomotion
|
Sources: Amigo / QuickGO |
|
Orthologs |
Species |
Human |
Mouse |
|
Entrez |
1132 |
12672 |
|
Ensembl |
ENSG00000180720 |
ENSMUSG00000040495 |
|
UniProt |
P08173 |
P32211 |
|
RefSeq (mRNA) |
NM_000741 |
NM_007699 |
|
RefSeq (protein) |
NP_000732 |
NP_031725 |
|
Location (UCSC) |
Chr 11:
46.41 – 46.41 Mb |
Chr 2:
91.92 – 91.93 Mb |
|
PubMed search |
[1] |
[2] |
|
|
The muscarinic acetylcholine receptor M4, also known as the cholinergic receptor, muscarinic 4 (CHRM4), is a protein that, in humans, is encoded by the CHRM4 gene.[1][2]
Contents
- 1 Function
- 2 Ligands
- 2.1 Orthosteric agonists
- 2.2 Allosteric Agonists
- 2.3 Antagonists
- 3 See also
- 4 References
- 5 Further reading
Function[edit]
The muscarinic cholinergic receptors belong to a larger family of G protein-coupled receptors. The functional diversity of these receptors is defined by the binding of acetylcholine and includes cellular responses such as adenylate cyclase inhibition, phosphoinositide degeneration, and potassium channel modulation. Muscarinic receptors mediate many effects of acetylcholine in the central and peripheral nervous system. The clinical implications of this receptor are unknown; however, mouse studies link its function to adenylyl cyclase inhibition.[1]
M4 muscarinic receptors function as inhibitory autoreceptors for acetylcholine. Activation of M4 receptors inhibits acetylcholine release in the striatum. The M2 subtype of acetylcholine receptor functions similarly as an inhibitory autoreceptor to acetylcholine release, albeit functioning actively primarily in the hippocampus and cerebral cortex.
Muscarinic acetylcholine receptors possess a regulatory effect on dopaminergic neurotransmission. Activation of M4 receptors in the striatum inhibit D1-induced locomotor stimulation in mice. M4 receptor-deficient mice exhibit increased locomotor simulation in response to D1 agonists, amphetamine and cocaine.[3][4][5] Neurotransmission in the striatum influences extrapyramidal motor control, thus alterations in M4 activity may contribute to conditions such as Parkinson's Disease.[6][7][8]
Ligands[edit]
Orthosteric agonists[edit]
- acetylcholine
- carbachol
- oxotremorine
Allosteric Agonists[edit]
- LY-2033298 [9]
- VU-0152100
- VU-0152099 [10]
Antagonists[edit]
- AFDX-384 (mixed M2/M4 antagonist, N-[2-[2-[(Dipropylamino)methyl]-1-piperidinyl]ethyl]-5,6-dihydro-6-oxo-11H-pyrido[2,3-b][1,4]benzodiazepine-11-carboxamide, CAS# 118290-27-0)
- Dicycloverine[11]
- Himbacine
- Mamba toxin 3[12]
- PD-102,807 (3,6a,11,14-Tetrahydro-9-methoxy-2-methyl-(12H)-isoquino[1,2-b]pyrrolo[3,2-f][1,3]benzoxazine-1-carboxylic acid ethyl ester, CAS# 23062-91-1)
- PD-0298029
- Tropicamide - moderate selectivity over other muscarinic subtypes (2-5x approx)[13]
See also[edit]
- Muscarinic acetylcholine receptor
References[edit]
- ^ a b "Entrez Gene: CHRM4 cholinergic receptor, muscarinic 4".
- ^ Grewal RP, Martinez M, Hoehe M, Bonner TI, Gershon ES, Detera-Wadleigh S (May 1992). "Genetic linkage mapping of the m4 human muscarinic receptor (CHRM4)". Genomics 13 (1): 239–40. doi:10.1016/0888-7543(92)90236-L. PMID 1577490.
- ^ Gomeza J, Zhang L, Kostenis E, Felder C, Bymaster F, Brodkin J, Shannon H, Xia B, Deng C, Wess J (August 1999). "Enhancement of D1 dopamine receptor-mediated locomotor stimulation in M(4) muscarinic acetylcholine receptor knockout mice". Proceedings of the National Academy of Sciences of the United States of America 96 (18): 10483–8. PMC 17915. PMID 10468635.
- ^ Jeon J, Dencker D, Wörtwein G, et al. (February 2010). "A subpopulation of neuronal M4 muscarinic acetylcholine receptors plays a critical role in modulating dopamine-dependent behaviors". J. Neurosci. 30 (6): 2396–405. doi:10.1523/JNEUROSCI.3843-09.2010. PMC 2824442. PMID 20147565.
- ^ Schmidt, L. S.; Thomsen, M.; Weikop, P.; Dencker, D.; Wess, J. R.; Woldbye, D. P. D.; Wortwein, G.; Fink-Jensen, A. (2011). "Increased cocaine self-administration in M4 muscarinic acetylcholine receptor knockout mice". Psychopharmacology 216 (3): 367–378. doi:10.1007/s00213-011-2225-4. PMID 21373792. edit
- ^ Langmead CJ, Watson J, Reavill C (February 2008). "Muscarinic acetylcholine receptors as CNS drug targets". Pharmacology & Therapeutics 117 (2): 232–43. doi:10.1016/j.pharmthera.2007.09.009. PMID 18082893.
- ^ Stein IS, Hell JW (June 2010). "CaMKII hunkers down on the muscarinic M4 receptor to help curb cocaine-induced hyperlocomotion". The EMBO Journal 29 (12): 1943–5. doi:10.1038/emboj.2010.105. PMC 2892364. PMID 20551968.
- ^ Guo ML, Mao LM, Wang JQ (December 2010). "Modulation of M4 muscarinic acetylcholine receptors by interacting proteins". Neuroscience Bulletin 26 (6): 469–73. PMC 3139403. PMID 21113197.
- ^ Chan WY, McKinzie DL, Bose S, et al. (2008). "Allosteric modulation of the muscarinic M4 receptor as an approach to treating schizophrenia". PNAS 105 (31): 10978–83. doi:10.1073/pnas.0800567105. PMC 2495016. PMID 18678919.
- ^ Brady AE, Jones CK, Bridges TM, et al. (2008). "Centrally active allosteric potentiators of the M4 muscarinic acetylcholine receptor reverse amphetamine-induced hyperlocomotor activity in rats". J. Pharmacol. Exp. Ther. 327 (3): 941–53. doi:10.1124/jpet.108.140350. PMC 2745822. PMID 18772318.
- ^ Teaktong T, Piggott MA, Mckeith IG, Perry RH, Ballard CG, Perry EK (June 2005). "Muscarinic M2 and M4 receptors in anterior cingulate cortex: relation to neuropsychiatric symptoms in dementia with Lewy bodies". Behavioural Brain Research 161 (2): 299–305. doi:10.1016/j.bbr.2005.02.019. PMID 15922057.
- ^ http://www.uniprot.org/uniprot/P81031
- ^ Lazareno S, Buckley NJ, Roberts FF (December 1990). "Characterization of muscarinic M4 binding sites in rabbit lung, chicken heart, and NG108-15 cells". Molecular Pharmacology 38 (6): 805–15. PMID 2250662.
Further reading[edit]
- Goyal RK; Underhill, Lisa H.; Goyal, Raj K. (1989). "Muscarinic receptor subtypes. Physiology and clinical implications.". N. Engl. J. Med. 321 (15): 1022–9. doi:10.1056/NEJM198910123211506. PMID 2674717.
- Brann MR, Ellis J, Jørgensen H, et al. (1994). "Muscarinic acetylcholine receptor subtypes: localization and structure/function.". Prog. Brain Res. 98: 121–7. doi:10.1016/S0079-6123(08)62388-2. PMID 8248499.
- Grewal RP, Martinez M, Hoehe M, et al. (1992). "Genetic linkage mapping of the m4 human muscarinic receptor (CHRM4).". Genomics 13 (1): 239–40. doi:10.1016/0888-7543(92)90236-L. PMID 1577490.
- Detera-Wadleigh SD, Wiesch D, Bonner TI (1989). "An SstI polymorphism for the human muscarinic acetylcholine receptor gene, m4 (CHRM 4).". Nucleic Acids Res. 17 (15): 6431. doi:10.1093/nar/17.15.6431. PMC 318330. PMID 2570410.
- Ashkenazi A, Ramachandran J, Capon DJ (1989). "Acetylcholine analogue stimulates DNA synthesis in brain-derived cells via specific muscarinic receptor subtypes.". Nature 340 (6229): 146–50. doi:10.1038/340146a0. PMID 2739737.
- Bonner TI, Buckley NJ, Young AC, Brann MR (1987). "Identification of a family of muscarinic acetylcholine receptor genes.". Science 237 (4814): 527–32. doi:10.1126/science.3037705. PMID 3037705.
- Bonner TI, Young AC, Brann MR, Buckley NJ (1990). "Cloning and expression of the human and rat m5 muscarinic acetylcholine receptor genes.". Neuron 1 (5): 403–10. doi:10.1016/0896-6273(88)90190-0. PMID 3272174.
- Peralta EG, Ashkenazi A, Winslow JW, et al. (1988). "Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors.". EMBO J. 6 (13): 3923–9. PMC 553870. PMID 3443095.
- van Koppen CJ, Lenz W, Nathanson NM (1993). "Isolation, sequence and functional expression of the mouse m4 muscarinic acetylcholine receptor gene.". Biochim. Biophys. Acta 1173 (3): 342–4. PMID 7916637.
- Haga K, Kameyama K, Haga T, et al. (1996). "Phosphorylation of human m1 muscarinic acetylcholine receptors by G protein-coupled receptor kinase 2 and protein kinase C.". J. Biol. Chem. 271 (5): 2776–82. doi:10.1074/jbc.271.5.2776. PMID 8576254.
- von der Kammer H, Mayhaus M, Albrecht C, et al. (1998). "Muscarinic acetylcholine receptors activate expression of the EGR gene family of transcription factors.". J. Biol. Chem. 273 (23): 14538–44. doi:10.1074/jbc.273.23.14538. PMID 9603968.
- Oldenhof J, Vickery R, Anafi M, et al. (1998). "SH3 binding domains in the dopamine D4 receptor.". Biochemistry 37 (45): 15726–36. doi:10.1021/bi981634. PMID 9843378.
- Sato KZ, Fujii T, Watanabe Y, et al. (1999). "Diversity of mRNA expression for muscarinic acetylcholine receptor subtypes and neuronal nicotinic acetylcholine receptor subunits in human mononuclear leukocytes and leukemic cell lines.". Neurosci. Lett. 266 (1): 17–20. doi:10.1016/S0304-3940(99)00259-1. PMID 10336173.
- Dias Neto E, Correa RG, Verjovski-Almeida S, et al. (2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags.". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3491–6. doi:10.1073/pnas.97.7.3491. PMC 16267. PMID 10737800.
- Wang H, Han H, Zhang L, et al. (2001). "Expression of multiple subtypes of muscarinic receptors and cellular distribution in the human heart.". Mol. Pharmacol. 59 (5): 1029–36. PMID 11306684.
- Buchli R, Ndoye A, Arredondo J, et al. (2002). "Identification and characterization of muscarinic acetylcholine receptor subtypes expressed in human skin melanocytes.". Mol. Cell. Biochem. 228 (1–2): 57–72. doi:10.1023/A:1013368509855. PMID 11855742.
- McClatchy DB, Knudsen CR, Clark BF, et al. (2002). "Novel interaction between the M4 muscarinic acetylcholine receptor and elongation factor 1A2". J. Biol. Chem. 277 (32): 29268–74. doi:10.1074/jbc.M203081200. PMID 12048193.
- Dean B, McLeod M, Keriakous D, et al. (2003). "Decreased muscarinic1 receptors in the dorsolateral prefrontal cortex of subjects with schizophrenia". Mol. Psychiatry 7 (10): 1083–91. doi:10.1038/sj.mp.4001199. PMID 12476323.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
Cell surface receptor: G protein-coupled receptors
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Class A:
Rhodopsin like |
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Class B: Secretin like |
Orphan
|
- GPR (56
- 64
- 97
- 98
- 110
- 111
- 112
- 113
- 114
- 115
- 116
- 123
- 124
- 125
- 126
- 128
- 133
- 143
- 144
- 155
- 157)
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Other
|
- Brain-specific angiogenesis inhibitor (1
- 2
- 3)
- Cadherin (1
- 2
- 3)
- Calcitonin
- CALCRL
- CD97
- Corticotropin-releasing hormone (1
- 2)
- EMR (1
- 2
- 3)
- Glucagon (GR
- GIPR
- GLP1R
- GLP2R)
- Growth hormone releasing hormone
- PACAPR1
- GPR
- Latrophilin (1
- 2
- 3
- ELTD1)
- Methuselah-like proteins
- Parathyroid hormone (1
- 2)
- Secretin
- Vasoactive intestinal peptide (1
- 2)
|
|
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Class C: Metabotropic
glutamate / pheromone |
Taste
|
- TAS1R (1
- 2
- 3)
- TAS2R (1
- 3
- 4
- 5
- 7
- 8
- 9
- 10
- 13
- 14
- 16
- 19
- 20
- 30
- 31
- 38
- 39
- 40
- 41
- 42
- 43
- 45
- 46
- 50
- 60)
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|
Other
|
- Calcium-sensing receptor
- GABA B (1
- 2)
- Glutamate receptor (Metabotropic glutamate (1
- 2
- 3
- 4
- 5
- 6
- 7
- 8))
- GPRC6A
- GPR (156
- 158
- 179)
- RAIG (1
- 2
- 3
- 4)
|
|
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Class F:
Frizzled / Smoothened |
Frizzled
|
- Frizzled (1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10)
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Smoothened
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B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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UpToDate Contents
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English Journal
- Modified expression of peripheral blood lymphocyte muscarinic cholinergic receptors in asthmatic children.
- Cherubini E1, Tabbì L1, Scozzi D1, Mariotta S1, Galli E2, Carello R2, Avitabile S2, Tayebati SK3, Amenta F3, De Vitis C4, Mancini R5, Ricci A6.
- Journal of neuroimmunology.J Neuroimmunol.2015 Jul 15;284:37-43. doi: 10.1016/j.jneuroim.2015.04.016. Epub 2015 May 1.
- Lymphocytes possess an independent cholinergic system. We assessed the expression of muscarinic cholinergic receptors in lymphocytes from 49 asthmatic children and 10 age matched controls using Western blot. We demonstrated that CD4+ and CD8+ T cells expressed M2 and M4 muscarinic receptors which de
- PMID 26025056
- The A- and B-type muscarinic acetylcholine receptors from Drosophila melanogaster couple to different second messenger pathways.
- Ren GR1, Folke J1, Hauser F1, Li S1, Grimmelikhuijzen CJ2.
- Biochemical and biophysical research communications.Biochem Biophys Res Commun.2015 Jul 10;462(4):358-64. doi: 10.1016/j.bbrc.2015.04.141. Epub 2015 May 9.
- Muscarinic acetylcholine receptors (mAChRs) are G protein-coupled receptors (GPCRs) that are activated by the agonists acetylcholine and muscarine and blocked by several antagonists, among them atropine. In mammals five mAChRs (m1-m5) exist of which m1, m3, and m5 are coupled to members of the Gq/11
- PMID 25964087
- Detection and quantification of allosteric modulation of endogenous m4 muscarinic acetylcholine receptor using impedance-based label-free technology in a neuronal cell line.
- Chen AN1, Malone DT1, Pabreja K1, Sexton PM1, Christopoulos A1, Canals M2.
- Journal of biomolecular screening.J Biomol Screen.2015 Jun;20(5):646-54. doi: 10.1177/1087057114563025. Epub 2014 Dec 22.
- Allosteric modulators of G protein-coupled receptors have the potential to achieve greater receptor subtype selectivity compared with ligands targeting the orthosteric site of this receptor family. However, the high attrition rate in GPCR drug discovery programs has highlighted the need to better ch
- PMID 25534830
Japanese Journal
- A case of thyroid storm with a markedly elevated level of circulating soluble interleukin-2 receptor complicated by multiple organ failure and disseminated intravascular coagulation syndrome
- Shimoda Yoko,Satoh Tetsurou,Takahashi Hiroki,Katano-Toki Akiko,Ozawa Atsushi,Tomaru Takuya,Horiguchi Norio,Kaira Kyoichi,Nishioka Masaki,Shibusawa Nobuyuki,Hashimoto Koshi,Wakino Shu,Mori Masatomo,Yamada Masanobu
- Endocrine Journal 61(7), 691-696, 2014
- … The patient exhibited impaired consciousness (E4V1M4 in Glasgow coma scale), high fever (39.3°C), and atrial flutter with a pulse rate 162/min, and was complicated by heart failure, acute hepatic failure, and disseminated intravascular coagulation syndrome (DIC). … His circulating level of soluble interleukin-2 receptor (sIL-2R), a serum marker of an activated immune response, was highly elevated (7,416 U/mL, reference range: 135-483). …
- NAID 130004677940
- Expression of Adrenergic and Cholinergic Receptors in Murine Renal Intercalated Cells
- JUN Jin-Gon,MAEDA Seishi,KUWAHARA-OTANI Sachi,TANAKA Koichi,HAYAKAWA Tetsu,SEKI Makoto
- Journal of Veterinary Medical Science 76(11), 1493-1500, 2014
- … We found that M-1 cells express a2 and b2 adrenergic receptor mRNA and the b2 receptor protein. … Further, b2 receptor-positive cells in the murine cortical collecting ducts also express AQP6, indicating that these cells are ICCs. … M-1 cells were found to express m1, m4 and m5 muscarinic receptor mRNAs and the m1 receptor protein. …
- NAID 130004677720
- TRPM4 Channels Mediate Hypertonicity-induced, Ca2+-impermeable, Non-selective Cation Currents in a Cervical Cancer Cell Line, HeLa Cells
- GOMI Simmon,NAKADA Tsutomu,KASHIHARA Toshihide,IKEDA Uichi,YAMADA Mitsuhiko
- 信州医学雑誌 62(1), 33-44, 2014
- … RT-PCR indicated that HeLa cells express transient receptor potential (TRP) C1, C6, M3, M4, M7, M8, V1 and V2 subunits which form non-selective cation channels. …
- NAID 130004551913
Related Links
- 2.2 Endocytic adaptor protein 2 (AP2) and M4R The agonist-induced M4R internalization is an important way to decrease the receptor efficacy after its activation. In this type of homo-desensitization process, an endocytic pathway ...
- Nomenclature Superfamily 7-Transmembrane receptors Family Acetylcholine Receptor Type Muscarinic cholinergic receptor Subtypes M4 Classification Numbers 2.1.ACH04 Alternate or Previous Names m4 Comments Until the ...
Related Pictures
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★リンクテーブル★
[★]
- 英
- M4 receptor
- 関
- M4レセプター
[★]
- 英
- M4 receptor
- 関
- M4受容体
[★]
[★]
急性骨髄単球性白血病 acute myelomonocytic leukemia AMMoL
[★]
メチオニン methionine