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M u s c a r i n i c a c e t y l c h o l i n e r e c e p t o r M 4
6 l a n g u a g e s
● ا ل ع ر ب ي ة ● E s p a ñ o l ● С р п с к и / s r p s k i ● S r p s k o h r v a t s k i / с р п с к о х р в а т с к и ● Т а т а р ч а / t a t a r ç a ● У к р а ї н с ь к а
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● D o w n l o a d a s P D F ● P r i n t a b l e v e r s i o n
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A p p e a r a n c e
F r o m W i k i p e d i a , t h e f r e e e n c y c l o p e d i a
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 .[5] [6]
Function
[ edit ]
M 4 muscarinic receptors are coupled to Gi/o heterotrimeric proteins.[7]
They function as inhibitory autoreceptors for acetylcholine. Activation of M4 acetylcholine release in the striatum . The M2 hippocampus and cerebral cortex .
Muscarinic acetylcholine receptors possess a regulatory effect on dopaminergic neurotransmission . Activation of M4 striatum inhibit D 1 locomotor stimulation in mice . M4 D 1 amphetamine and cocaine .[8] [9] [10] extrapyramidal motor control , thus alterations in M4 Parkinson's disease .[11] [12] [13]
Ligands
[ edit ]
Orthosteric agonists
[ edit ] VU-0152100
Positive allosteric modulators
[ edit ]
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 [21]
Himbacine
Mamba toxin 3[22]
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)[23]
Diphenhydramine
See also
[ edit ]
References
[ edit ]
^ a b c GRCm38: Ensembl release 89: ENSMUSG00000040495 – Ensembl , May 2017
^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ "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 .
^ Qin K, Dong C, Wu G, Lambert NA (2011). "Inactive-state preassembly of G(q )-coupled receptors and G(q ) heterotrimers" . Nat. Chem. Biol . 7 10 ): 740–7. doi :10.1038/nchembio.642 . PMC 3177959 PMID 21873996 .
^ 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. Bibcode :1999PNAS...9610483G . doi :10.1073/pnas.96.18.10483 PMC 17915 PMID 10468635 .
^ Jeon J, Dencker D, Wörtwein G, Woldbye DP, Cui Y, Davis AA, Levey AI, Schütz G, Sager TN, Mørk A, Li C, Deng CX, Fink-Jensen A, Wess J (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 LS, Thomsen M, Weikop P, Dencker D, Wess J, Woldbye DP, 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 . PMC 3899540 PMID 21373792 .
^ 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. doi :10.1007/s12264-010-0933-0 . PMC 3139403 PMID 21113197 .
^ Chan WY, McKinzie DL, Bose S, Mitchell SN, Witkin JM, Thompson RC, Christopoulos A, Lazareno S, Birdsall NJ, Bymaster FP, Felder CC (2008). "Allosteric modulation of the muscarinic M4 receptor as an approach to treating schizophrenia" . PNAS . 105 (31 ): 10978–83. Bibcode :2008PNAS..10510978C . doi :10.1073/pnas.0800567105 PMC 2495016 PMID 18678919 .
^ a b Brady AE, Jones CK, Bridges TM, Kennedy JP, Thompson AD, Heiman JU, Breininger ML, Gentry PR, Yin H, Jadhav SB, Shirey JK, Conn PJ, Lindsley CW (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 .
^ Dencker D, Weikop P, Sørensen G, et al. (2012). "An allosteric enhancer of M4 . Psychopharmacology . 224 (2 ): 277–87. doi :10.1007/s00213-012-2751-8 . PMC 3914671 PMID 22648127 .
^ Byun NE, Grannan M, Bubser M, et al. (2014). "Antipsychotic drug-like effects of the selective M4 muscarinic acetylcholine receptor positive allosteric modulator VU0152100" . Neuropsychopharmacology . 39 7 ): 1578–93. doi :10.1038/npp.2014.2 . PMC 4023154 PMID 24442096 .
^ Galloway CR, Lebois EP, Shagarabi SL, Hernandez NA, Manns JR (2014). "Effects of selective activation of M1 and M4 muscarinic receptors on object recognition memory performance in rats". Pharmacology . 93 doi :10.1159/000357682 . PMID 24480931 . S2CID 10402346 .
^ Pancani T, Bolarinwa C, Smith Y, Lindsley CW, Conn PJ, Xiang Z (2014). "M4 mAChR-mediated modulation of glutamatergic transmission at corticostriatal synapses" . ACS Chem Neurosci . 5 4 ): 318–24. doi :10.1021/cn500003z . PMC 3990947 PMID 24528004 .
^ Huynh T, Valant C, Crosby IT, Sexton PM, Christopoulos A, Capuano B (2013). "Probing structural requirements of positive allosteric modulators of the M4 muscarinic receptor". J. Med. Chem . 56 20 ): 8196–200. doi :10.1021/jm401032k . PMID 24074052 .
^ 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 . S2CID 34247659 .
^ "Muscarinic toxin 3 - Dendroaspis angusticeps (Eastern green mamba)" .
^ 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 ]
Brann MR, Ellis J, Jørgensen H, Hill-Eubanks D, Jones SV (1993). "Muscarinic acetylcholine receptor subtypes: localization and structure/function". Prog. Brain Res . 98 doi :10.1016/S0079-6123(08 )62388-2 . PMID 8248499 .
Grewal RP, Martinez M, Hoehe M, Bonner TI, Gershon ES, Detera-Wadleigh S (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. Bibcode :1989Natur.340..146A . doi :10.1038/340146a0 . PMID 2739737 . S2CID 4312544 .
Bonner TI, Buckley NJ, Young AC, Brann MR (1987). "Identification of a family of muscarinic acetylcholine receptor genes" . Science . 237 (4814): 527–32. Bibcode :1987Sci...237..527B . 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 . S2CID 833230 .
Peralta EG, Ashkenazi A, Winslow JW, Smith DH, Ramachandran J, Capon DJ (1988). "Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors" . EMBO J . 6 13 ): 3923–9. doi :10.1002/j.1460-2075.1987.tb02733.x . 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. doi :10.1016/0167-4781(93 )90135-z . PMID 7916637 .
Haga K, Kameyama K, Haga T, Kikkawa U, Shiozaki K, Uchiyama H (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, Enderich J, Wegner M, Nitsch RM (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, Oak J, Ray A, Schoots O, Pawson T, von Zastrow M, Van Tol HH (1998). "SH3 binding domains in the dopamine D4 receptor" (PDF) . Biochemistry . 37 45 ): 15726–36. doi :10.1021/bi981634+ . PMID 9843378 .
Sato KZ, Fujii T, Watanabe Y, Yamada S, Ando T, Kazuko F, Kawashima K (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 . S2CID 43548155 .
Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ, Simpson AJ (2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags" . Proc. Natl. Acad. Sci. U.S.A . 97 7 ): 3491–6. Bibcode :2000PNAS...97.3491D . doi :10.1073/pnas.97.7.3491 PMC 16267 PMID 10737800 .
Wang H, Han H, Zhang L, Shi H, Schram G, Nattel S, Wang Z (2001). "Expression of multiple subtypes of muscarinic receptors and cellular distribution in the human heart". Mol. Pharmacol . 59 5 ): 1029–36. doi :10.1124/mol.59.5.1029 . PMID 11306684 .
Buchli R, Ndoye A, Arredondo J, Webber RJ, Grando SA (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 . S2CID 10788646 .
McClatchy DB, Knudsen CR, Clark BF, Kahn RA, Hall RA, Levey AI (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, McKenzie J, Scarr E (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 .
External links
[ edit ]
Overview of all the structural information available in the PDB for UniProt : P08173 PDBe-KB .
This article incorporates text from the United States National Library of Medicine , which is in the public domain .
t
e
mAChRs Tooltip Muscarinic acetylcholine receptors
Agonists
Antagonists
3-Quinuclidinyl benzilate
4-DAMP
Aclidinium bromide (+formoterol )
Abediterol
AF-DX 250
AF-DX 384
Ambutonium bromide
Anisodamine
Anisodine
Antihistamines (first-generation) (e.g., brompheniramine , buclizine , captodiame , chlorphenamine (chlorpheniramine) , cinnarizine , clemastine , cyproheptadine , dimenhydrinate , dimetindene , diphenhydramine , doxylamine , meclizine , mequitazine , perlapine , phenindamine , pheniramine , phenyltoloxamine , promethazine , propiomazine , triprolidine )
AQ-RA 741
Atropine
Atropine methonitrate
Atypical antipsychotics (e.g., clozapine , fluperlapine , olanzapine (+fluoxetine ), rilapine , quetiapine , tenilapine , zotepine )
Benactyzine
Benzatropine (benztropine)
Benzilone
Benzilylcholine mustard
Benzydamine
Bevonium
BIBN 99
Biperiden
Bornaprine
Camylofin
CAR-226,086
CAR-301,060
CAR-302,196
CAR-302,282
CAR-302,368
CAR-302,537
CAR-302,668
Caramiphen
Cimetropium bromide
Clidinium bromide
Cloperastine
CS-27349
Cyclobenzaprine
Cyclopentolate
Darifenacin
DAU-5884
Desfesoterodine
Dexetimide
DIBD
Dicycloverine (dicyclomine)
Dihexyverine
Difemerine
Diphemanil metilsulfate
Ditran
Drofenine
EA-3167
EA-3443
EA-3580
EA-3834
Emepronium bromide
Etanautine
Etybenzatropine (ethybenztropine)
Fenpiverinium
Fentonium bromide
Fesoterodine
Flavoxate
Glycopyrronium bromide (+beclometasone/formoterol , +indacaterol , +neostigmine )
Hexahydrodifenidol
Hexahydrosiladifenidol
Hexbutinol
Hexocyclium
Himbacine
HL-031,120
Homatropine
Imidafenacin
Ipratropium bromide (+salbutamol )
Isopropamide
J-104,129
Hyoscyamine
Mamba toxin 3
Mamba toxin 7
Mazaticol
Mebeverine
Meladrazine
Mepenzolate
Methantheline
Methoctramine
Methylatropine
Methylhomatropine
Methylscopolamine
Metixene
Muscarinic toxin 7
N-Ethyl-3-piperidyl benzilate
N-Methyl-3-piperidyl benzilate
Nefopam
Octatropine methylbromide (anisotropine methylbromide)
Orphenadrine
Otenzepad (AF-DX 116)
Otilonium bromide
Oxapium iodide
Oxitropium bromide
Oxybutynin
Oxyphencyclimine
Oxyphenonium bromide
PBID
PD-102,807
PD-0298029
Penthienate
Pethidine
pFHHSiD
Phenglutarimide
Phenyltoloxamine
Pipenzolate bromide
Piperidolate
Pirenzepine
Piroheptine
Pizotifen
Poldine
Pridinol
Prifinium bromide
Procyclidine
Profenamine (ethopropazine)
Propantheline bromide
Propiverine
Quinidine
3-Quinuclidinyl thiochromane-4-carboxylate
Revefenacin
Rociverine
RU-47,213
SCH-57,790
SCH-72,788
SCH-217,443
Scopolamine (hyoscine)
Scopolamine butylbromide (hyoscine butylbromide)
Silahexacyclium
Sofpironium bromide
Solifenacin
SSRIs Tooltip Selective serotonin reuptake inhibitors (e.g., femoxetine , paroxetine )
Telenzepine
Terodiline
Tetracyclic antidepressants (e.g., amoxapine , maprotiline , mianserin , mirtazapine )
Tiemonium iodide
Timepidium bromide
Tiotropium bromide
Tiquizium bromide
Tofenacin
Tolterodine
Tricyclic antidepressants (e.g., amitriptyline (+perphenazine ), amitriptylinoxide , butriptyline , cidoxepin , clomipramine , desipramine , desmethyldesipramine , dibenzepin , dosulepin (dothiepin) , doxepin , imipramine , lofepramine , nitroxazepine , northiaden (desmethyldosulepin) , nortriptyline , protriptyline , quinupramine , trimipramine )
Tridihexethyl
Trihexyphenidyl
Trimebutine
Tripitamine (tripitramine)
Tropacine
Tropatepine
Tropicamide
Trospium chloride
Typical antipsychotics (e.g., chlorpromazine , chlorprothixene , cyamemazine (cyamepromazine) , loxapine , mesoridazine , thioridazine )
Umeclidinium bromide (+vilanterol )
WIN-2299
Xanomeline
Zamifenacin
Precursors (and prodrugs )
See also
Receptor/signaling modulators
Nicotinic acetylcholine receptor modulators
Acetylcholine metabolism/transport modulators
R e t r i e v e d f r o m " https://en.wikipedia.org/w/index.php?title=Muscarinic_acetylcholine_receptor_M4&oldid=1123505101 " C a t e g o r i e s : ● G e n e s o n h u m a n c h r o m o s o m e 1 1 ● G p r o t e i n - c o u p l e d r e c e p t o r s ● H u m a n p r o t e i n s ● M u s c a r i n i c a c e t y l c h o l i n e r e c e p t o r s H i d d e n c a t e g o r i e s : ● A r t i c l e s w i t h s h o r t d e s c r i p t i o n ● S h o r t d e s c r i p t i o n i s d i f f e r e n t f r o m W i k i d a t a ● W i k i p e d i a a r t i c l e s i n c o r p o r a t i n g t e x t f r o m t h e U n i t e d S t a t e s N a t i o n a l L i b r a r y o f M e d i c i n e
● T h i s p a g e w a s l a s t e d i t e d o n 2 4 N o v e m b e r 2 0 2 2 , a t 0 3 : 1 2 ( U T C ) . ● T e x t i s a v a i l a b l e u n d e r t h e C r e a t i v e C o m m o n s A t t r i b u t i o n - S h a r e A l i k e L i c e n s e 4 . 0 ;
a d d i t i o n a l t e r m s m a y a p p l y . B y u s i n g t h i s s i t e , y o u a g r e e t o t h e T e r m s o f U s e a n d P r i v a c y P o l i c y . W i k i p e d i a ® i s a r e g i s t e r e d t r a d e m a r k o f t h e W i k i m e d i a F o u n d a t i o n , I n c . , a n o n - p r o f i t o r g a n i z a t i o n . ● P r i v a c y p o l i c y ● A b o u t W i k i p e d i a ● D i s c l a i m e r s ● C o n t a c t W i k i p e d i a ● C o d e o f C o n d u c t ● D e v e l o p e r s ● S t a t i s t i c s ● C o o k i e s t a t e m e n t ● M o b i l e v i e w
