Muscarinic acetylcholine receptor M1: Difference between revisions

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{{Wrongtitle|title=Muscarinic acetylcholine receptor M<sub>1</sub>}}
{{DISPLAYTITLE:Muscarinic acetylcholine receptor M<sub>1</sub>}}
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{{Infobox_gene}}
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The '''muscarinic acetylcholine receptor M<sub>1</sub>''', also known as the '''cholinergic receptor, muscarinic 1''', is a [[muscarinic receptor]] that in humans is encoded by the ''CHRM1'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: CHRM1 cholinergic receptor, muscarinic 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1128| accessdate = }}</ref> It is localized to [[11q13]].<ref name="entrez"/>
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This receptor is found mediating slow [[excitatory postsynaptic potential|EPSP]] at the ganglion in the postganglionic nerve,<ref name="Messer_2000">{{cite web|url=http://www.neurosci.pharm.utoledo.edu/MBC3320/acetylcholine.htm |title=Acetylcholine |accessdate=2007-10-27 |vauthors=Messer WS |date=2000-01-20 |publisher=University of Toledo |deadurl=yes |archiveurl=https://web.archive.org/web/20071014020222/http://www.neurosci.pharm.utoledo.edu/MBC3320/acetylcholine.htm |archivedate=14 October 2007 }}</ref> is common in [[exocrine gland]]s and in the CNS.<ref name="isbn1-55009-109-3">{{cite book | last = Johnson | first = Gordon | name-list-format = vanc | title = PDQ Pharmacology | publisher = BC Decker Inc | location = Hamilton, Ontario | year = 2002 | edition = 2nd | pages = 311 pages | isbn = 1-55009-109-3 }}</ref><ref name="Richelson_2000">{{cite book | editor-first1 = Floyd E. | editor-last1 = Bloom | editor-first2 = David J. | editor-last2 = Kupfer | title = Psychopharmacology: the fourth generation of progress: an official publication of the American College of Neuropsychopharmacology | first = Elliott | last = Richelson | name-list-format = vanc | chapter = Cholinergic Transduction | chapter-url = http://www.acnp.org/g4/GN401000011/Default.htm | accessdate = 2007-10-27 | date = 1995 | publisher = Lippincott Williams & Wilkins | location = New York | isbn = 978-0781701662 | edition = Fourth }}</ref>
{{GNF_Protein_box
| image = 
| image_source = 
| PDB =
| Name = Cholinergic receptor, muscarinic 1
| HGNCid = 1950
| Symbol = CHRM1
| AltSymbols =; HM1; M1; MGC30125
| OMIM = 118510
| ECnumber = 
| Homologene = 20189
| MGIid = 88396
| Function = {{GNF_GO|id=GO:0001584 |text = rhodopsin-like receptor activity}} {{GNF_GO|id=GO:0004435 |text = phosphoinositide phospholipase C activity}} {{GNF_GO|id=GO:0004872 |text = receptor activity}} {{GNF_GO|id=GO:0004981 |text = muscarinic acetylcholine receptor activity}}
| Component = {{GNF_GO|id=GO:0005624 |text = membrane fraction}} {{GNF_GO|id=GO:0005886 |text = plasma membrane}} {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}} {{GNF_GO|id=GO:0045211 |text = postsynaptic membrane}}
| Process = {{GNF_GO|id=GO:0006464 |text = protein modification process}} {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007205 |text = protein kinase C activation}} {{GNF_GO|id=GO:0007207 |text = muscarinic acetylcholine receptor, phospholipase C activating pathway}} {{GNF_GO|id=GO:0007213 |text = acetylcholine receptor signaling, muscarinic pathway}} {{GNF_GO|id=GO:0007399 |text = nervous system development}} {{GNF_GO|id=GO:0008283 |text = cell proliferation}} {{GNF_GO|id=GO:0008284 |text = positive regulation of cell proliferation}} {{GNF_GO|id=GO:0040012 |text = regulation of locomotion}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 1128
    | Hs_Ensembl = ENSG00000168539
    | Hs_RefseqProtein = NP_000729
    | Hs_RefseqmRNA = NM_000738
    | Hs_GenLoc_db =
    | Hs_GenLoc_chr = 11
    | Hs_GenLoc_start = 62432728
    | Hs_GenLoc_end = 62445588
    | Hs_Uniprot = P11229
    | Mm_EntrezGene = 12669
    | Mm_Ensembl = ENSMUSG00000032773
    | Mm_RefseqmRNA = NM_007698
    | Mm_RefseqProtein = NP_031724
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 19
    | Mm_GenLoc_start = 8731396
    | Mm_GenLoc_end = 8748612
    | Mm_Uniprot = Q52KQ0
  }}
}}
The '''muscarinic acetylcholine receptor M<sub>1</sub>''', also known as the '''cholinergic receptor, muscarinic 1''', is a [[muscarinic receptor]].


This receptor is found mediating slow [[excitatory postsynaptic potential|EPSP]] at the ganglion in the postganglionic nerve,<ref name="Messer_2000">{{cite web |url= http://www.neurosci.pharm.utoledo.edu/MBC3320/acetylcholine.htm |title= Acetylcholine|accessdate=2007-10-27 |author= Messer, Jr, WS | date= 2000-01-20 |publisher= University of Toledo }}</ref> is common in [[exocrine gland]]s and in the CNS.<ref name="isbn1-55009-109-3">{{cite book | author = Johnson, Gordon | title = PDQ Pharmacology | publisher = BC Decker Inc | location = Hamilton, Ontario | year = 2002 | edition = 2nd ed. | pages = 311 pages | isbn = 1-55009-109-3 | oclc = | doi = }}</ref><ref name="Richelson_2000">{{cite web |url= http://www.acnp.org/g4/GN401000011/Default.htm |title= Cholinergic Transduction, Psychopharmacology - The Fourth Generation of Progress |accessdate=2007-10-27 |author = Richelson, Elliott | date= 2000 |publisher= American College of Neuropsychopharmacology }}</ref>  
It is predominantly found bound to G proteins of class [[Gq alpha subunit|G<sub>q</sub>]]<ref name="Kou Qin">{{cite journal | vauthors = Qin K, Dong C, Wu G, Lambert NA | title = Inactive-state preassembly of Gq-coupled receptors and Gq heterotrimers | journal = Nature Chemical Biology | volume = 7 | issue = 11 | pages = 740–747 | date = August 2011 | pmid = 21873996 | doi = 10.1038/nchembio.642 | pmc = 3177959 }}</ref><ref name="pmid8645172">{{cite journal | vauthors = Burford NT, Nahorski SR | title = Muscarinic m1 receptor-stimulated adenylate cyclase activity in Chinese hamster ovary cells is mediated by Gs alpha and is not a consequence of phosphoinositidase C activation | journal = Biochem. J. | volume = 315 | issue = Pt 3 | pages = 883–8 | year = 1996 | pmid = 8645172 | pmc = 1217289 | doi = | url = http://www.biochemj.org/bj/315/bj3150883.htm }}</ref> that use upregulation of [[phospholipase]] C and, therefore, [[inositol trisphosphate]] and intracellular calcium as a signalling pathway. A receptor so bound would not be susceptible to [[Cholera toxin|CTX]] or [[Pertussis toxin|PTX]]. However, G<sub>i</sub> (causing a downstream decrease in [[Cyclic adenosine monophosphate|cAMP]]) and G<sub>s</sub> (causing an increase in cAMP) have also been shown to be involved in interactions in certain tissues, and so would be susceptible to PTX and CTX respectively.


It is predominantly found bound to G proteins of class [[Gq alpha subunit|G<sub>q</sub>]]<ref name="pmid8645172">{{cite journal | author = Burford NT, Nahorski SR | title = Muscarinic m1 receptor-stimulated adenylate cyclase activity in Chinese hamster ovary cells is mediated by Gs alpha and is not a consequence of phosphoinositidase C activation | journal = Biochem. J. | volume = 315 ( Pt 3) | issue = | pages = 883–8 | year = 1996 | pmid = 8645172 | doi = | issn = | url =  http://www.biochemj.org/bj/315/bj3150883.htm }}</ref> which use upregulation of [[phospholipase]] C and therefore [[inositol trisphosphate]] and intracellular calcium as a signalling pathway. A receptor so bound would not be susceptible to CTX or PTX. However, G<sub>i</sub> (causing a downstream decrease in [[cAMP]]) and G<sub>s</sub> (causing an increase in cAMP) have also been shown to be involved in interactions in certain tissues, and so would be susceptible to PTX and CTX respectively.
==Effects==
*[[excitatory postsynaptic potential|EPSP]] in [[autonomic ganglia]]{{citation needed|date=October 2014}}
* Secretion of [[catecholamine]]s from the [[adrenal medulla]]<ref>{{cite journal | vauthors = Harada K, Matsuoka H, Miyata H, Matsui M, Inoue M | title = Identification of muscarinic receptor subtypes involved in catecholamine secretion in adrenal medullary chromaffin cells by genetic deletion | journal = British Journal of Pharmacology | volume = 172 | issue = 5 | pages = 1348–59 | date = Mar 2015 | pmid = 25393049 | doi = 10.1111/bph.13011 | pmc=4337706}}</ref>
* Secretion from [[salivary gland]]s
* [[Gastric acid]] secretion from [[stomach]]<ref name="entrez"/>
* In [[central nervous system|CNS]] (memory?)<ref name="Rang"/>
* Vagally-induced [[bronchoconstriction]]<ref name="entrez"/>
* Mediating [[Olfaction|olfactory]] behaviors (e.g. [[aggression]], [[mating]])<ref>{{cite journal | vauthors = Smith RS, Hu R, DeSouza A, Eberly CL, Krahe K, Chan W, Araneda RC | title = Differential Muscarinic Modulation in the Olfactory Bulb | journal = The Journal of Neuroscience | volume = 35 | issue = 30 | pages = 10773–85 | date = Jul 2015 | pmid = 26224860 | doi = 10.1523/JNEUROSCI.0099-15.2015 | pmc=4518052}}</ref>
 
== Orthologs ==
 
A structural homolog of M1 receptor is expressed in unicellular eukaryotes, such as ''[[Acanthamoeba|Acanthamoeba castellanii]]''.<ref name="pmid27601178">{{cite journal | vauthors = Baig AM, Ahmad HR | title = Evidence of a M1-muscarinic GPCR homolog in unicellular eukaryotes: featuring Acanthamoeba spp bioinformatics 3D-modelling and experimentations | journal = Journal of Receptor and Signal Transduction Research | volume = | issue = | pages = 1–9 | year = 2016 | pmid = 27601178 | doi = 10.1080/10799893.2016.1217884 }}</ref> and ''[[Naegleria fowleri]]''.<ref name="pmid27447543">{{cite journal | vauthors = Baig AM | title = Primary Amoebic Meningoencephalitis: Neurochemotaxis and Neurotropic Preferences of Naegleria fowleri | journal = ACS Chemical Neuroscience | volume = 7 | issue = 8 | pages = 1026–9 | year = 2016 | pmid = 27447543 | doi = 10.1021/acschemneuro.6b00197 }}</ref> The receptor antagonists of M1 receptors have shown to be exert anti-proliferative effects on these amoebae.
 
== Mechanism ==


==Effects==
It couples to [[Gq alpha subunit|G<sub>q</sub>]], and, to a small extent, [[Gi alpha subunit|G<sub>i</sub>]] and [[Gs alpha subunit|G<sub>s</sub>]]. This results in slow [[EPSP]] and decreased [[potassium|K<sup>+</sup>]] conductance.<ref name="Rang"/><ref>{{cite journal | vauthors = Uchimura N, North RA | title = Muscarine reduces inwardly rectifying potassium conductance in rat nucleus accumbens neurones | journal = J. Physiol. | volume = 422 | issue = 1 | pages = 369–80 | date = 1 March 1990 | pmid = 1693682 | pmc = 1190137 | url = http://www.jphysiol.org/cgi/pmidlookup?view=long&pmid=1693682 | doi=10.1113/jphysiol.1990.sp017989}}</ref> It is preassembled to the G<sub>q</sub> heterotrimer through a polybasic [[C-terminus|c-terminal domain]].<ref name="Kou Qin"/>
*[[excitatory postsynaptic potential|EPSP]] in [[autonomic ganglia]]
 
* secretion from [[salivary gland]]s
==Ligands==
* [[gastric acid]] secretion from [[stomach]]<ref name="entrez"/>
* In [[central nervous system|CNS]] (memory?) <ref name=Rang/>  
* vagally-induced [[bronchoconstriction]]<ref name="entrez"/>


==Mechanism==
===Agonists===
It couples to [[Gq alpha subunit|G<sub>q</sub>]], and, to a small extent, [[Gi alpha subunit|G<sub>i</sub>]] and[[Gs alpha subunit|G<sub>s</sub>]]. This results in slow [[EPSP]] and decreased[[potassium|K<sup>+</sup>]] conductance <ref name=Rang/><ref>[http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1190137 PUBMED] - Muscarine reduces inwardly rectifying potassium conductance in rat ... </ref>
{{div col|colwidth=20em}}
* [[acetylcholine]]
* [[carbachol]]<ref name="Rang">{{cite book |vauthors=Rang HP, Dale MM, Ritter JM, Moore PK |year=2003 |title= Pharmacology | chapter =10 | edition = 5th |page=139 | publisher = Elsevier Churchill Livingstone | location = | isbn=0-443-07145-4}}</ref>
* [[cevimeline]]
* [[muscarine]]
* [[oxotremorine]]
* [[pilocarpine]]<ref name="pmid9371842">{{cite journal | vauthors = Hamilton SE, Loose MD, Qi M, Levey AI, Hille B, McKnight GS, Idzerda RL, Nathanson NM | title = Disruption of the m1 receptor gene ablates muscarinic receptor-dependent M current regulation and seizure activity in mice | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 94 | issue = 24 | pages = 13311–6 | year = 1997 | pmid = 9371842 | pmc = 24305 | doi = 10.1073/pnas.94.24.13311| url = http://www.pnas.org/content/94/24/13311.full.pdf }}</ref>  
* [[vedaclidine]]
* [[xanomeline]]
* [[77-LH-28-1]] - brain penetrant selective M<sub>1</sub> allosteric agonist
* [[CDD-0097]]
* [[McN-A-343]] - mixed M1/M4 agonist<ref name="Rang"/>
* [[L-689]], [[L-660]] - mixed M1/M3 agonist
{{Div col end}}


==Agonists==  
===Allosteric modulators===
*[[acetylcholine]]
*[[benzylquinolone carboxylic acid]]<ref name="pmid19906975">{{cite journal | vauthors = Shirey JK, Brady AE, Jones PJ, Davis AA, Bridges TM, Kennedy JP, Jadhav SB, Menon UN, Xiang Z, Watson ML, Christian EP, Doherty JJ, Quirk MC, Snyder DH, Lah JJ, Levey AI, Nicolle MM, Lindsley CW, Conn PJ | title = A selective allosteric potentiator of the M1 muscarinic acetylcholine receptor increases activity of medial prefrontal cortical neurons and restores impairments in reversal learning | journal = J. Neurosci. | volume = 29 | issue = 45 | pages = 14271–86 | date = November 2009 | pmid = 19906975 | pmc = 2811323 | doi = 10.1523/JNEUROSCI.3930-09.2009 }}</ref>
*[[oxotremorine]]
*[[BQZ-12]]<ref name="pmid27991860">{{cite journal | vauthors = Bradley SJ, Bourgognon JM, Sanger HE, Verity N, Mogg AJ, White DJ, Butcher AJ, Moreno JA, Molloy C, Macedo-Hatch T, Edwards JM, Wess J, Pawlak R, Read DJ, Sexton PM, Broad LM, Steinert JR, Mallucci GR, Christopoulos A, Felder CC, Tobin AB | title = M1 muscarinic allosteric modulators slow prion neurodegeneration and restore memory loss | journal = The Journal of Clinical Investigation | volume = 127 | issue = 2 | pages = 487–499 | year = 2017 | pmid = 27991860 | pmc = 5272187 | doi = 10.1172/JCI87526 }}</ref>
*[[carbachol]]<ref name=Rang>{{cite book | first = | last =Rang HP, Dale MM, Ritter JM, Moore PK| authorlink = | coauthors = | year = 2003| month = | title = Pharmacology | chapter = Ch. 10 | editor = | others = | edition = 5<sup>th</sup> edition | pages = page 139 | publisher = Elsevier Churchill Livingstone| location = | id = ISBN 0-443-07145-4| url = }}</ref>
*[[VU-0090157]]<ref name="pmid19047481">{{cite journal | vauthors = Marlo JE, Niswender CM, Days EL, Bridges TM, Xiang Y, Rodriguez AL, Shirey JK, Brady AE, Nalywajko T, Luo Q, Austin CA, Williams MB, Kim K, Williams R, Orton D, Brown HA, Lindsley CW, Weaver CD, Conn PJ | title = Discovery and characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity | journal = Mol. Pharmacol. | volume = 75 | issue = 3 | pages = 577–88 | year = 2008 | pmid = 19047481 | pmc = 2684909 | doi = 10.1124/mol.108.052886 }}</ref>
*[[McNA343]]<ref name=Rang/>  
*[[VU-0029767]]<ref name="pmid19047481"/>
*[<sup>3</sup>H]PT-1284- M1-selective PAM Radioligand<ref>{{Cite journal|last=Smith|first=Deborah L.|last2=Davoren|first2=Jennifer E.|last3=Edgerton|first3=Jeremy R.|last4=Lazzaro|first4=John T.|last5=Lee|first5=Che-Wah|last6=Neal|first6=Sarah|last7=Zhang|first7=Lei|last8=Grimwood|first8=Sarah|date=2016-09-01|title=Characterization of a Novel M1 Muscarinic Acetylcholine Receptor Positive Allosteric Modulator Radioligand, [3H]PT-1284|url=http://molpharm.aspetjournals.org/content/90/3/177|journal=Molecular Pharmacology|language=en|volume=90|issue=3|pages=177–187|doi=10.1124/mol.116.104737|issn=0026-895X|pmid=27382013}}</ref>


==Antagonists==
===Antagonists===
*[[atropine]]<ref name=Rang/>
{{div col|colwidth=20em}}
*[[dicycloverine]]<ref name=Rang/>
*[[atropine]]<ref name="Rang"/>
*[[tolterodine]]<ref name=Rang/>
*[[dicycloverine]]<ref name="Rang"/>
*[[oxybutynin]]<ref name=Rang/>
*[[hyoscyamine]]<ref>{{cite web | author1 = Edwards Pharmaceuticals, Inc. | author2 = Belcher Pharmaceuticals, Inc. | title = DailyMed | publisher = U.S. National Library of Medicine | date = May 2010 | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=f33a4774-9fbb-4782-a7e1-068e83b7504d | accessdate = January 13, 2013}}</ref>
*[[ipratropium]]<ref name=Rang/>
*[[ipratropium]]<ref name="Rang"/>
*[[mamba toxin]] MT7<ref name=Rang/>
*[[mamba toxin]] [[muscarinic toxin 7]] (MT7)<ref name="Rang"/>
*[[olanzapine]]
*[[pirenzepine]]
*[[pirenzepine]]
*[[oxybutynin]]<ref name="Rang"/>
*[[Benzatropine]]
*[[telenzepine]]
*[[telenzepine]]
*[[tolterodine]]<ref name="Rang"/>
{{Div col end}}


==Gene==
== See also ==
The receptor is encoded by human [[gene]] '''CHRM1'''.<ref name="entrez">{{cite web | title = Entrez Gene: CHRM1 cholinergic receptor, muscarinic 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1128| accessdate = }}</ref> It is localized to [[11q13]].<ref name="entrez"/>
* [[Muscarinic acetylcholine receptor]]


==See also==
== References ==
* [[Muscarinic acetylcholine receptor]]
{{Reflist|33em}}
 
== Further reading ==
{{Refbegin|35em}}
* {{cite journal | vauthors = Goyal RK | title = Muscarinic receptor subtypes. Physiology and clinical implications. | journal = N. Engl. J. Med. | volume = 321 | issue = 15 | pages = 1022–9 | year = 1989 | pmid = 2674717 | doi = 10.1056/NEJM198910123211506 }}
* {{cite journal | vauthors = Brann MR, Ellis J, Jørgensen H, Hill-Eubanks D, Jones SV | title = Muscarinic acetylcholine receptor subtypes: localization and structure/function. | journal = Prog. Brain Res. | volume = 98 | issue =  | pages = 121–7 | year = 1994 | pmid = 8248499 | doi = 10.1016/S0079-6123(08)62388-2 }}
* {{cite journal | vauthors = Nitsch RM, Slack BE, Wurtman RJ, Growdon JH | title = Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors. | journal = Science | volume = 258 | issue = 5080 | pages = 304–7 | year = 1992 | pmid = 1411529 | doi = 10.1126/science.1411529 }}
* {{cite journal | vauthors = Arden JR, Nagata O, Shockley MS, Philip M, Lameh J, Sadée W | title = Mutational analysis of third cytoplasmic loop domains in G-protein coupling of the HM1 muscarinic receptor. | journal = Biochem. Biophys. Res. Commun. | volume = 188 | issue = 3 | pages = 1111–5 | year = 1992 | pmid = 1445347 | doi = 10.1016/0006-291X(92)91346-R }}
* {{cite journal | vauthors = Gutkind JS, Novotny EA, Brann MR, Robbins KC | title = Muscarinic acetylcholine receptor subtypes as agonist-dependent oncogenes. | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 88 | issue = 11 | pages = 4703–7 | year = 1991 | pmid = 1905013 | pmc = 51734 | doi = 10.1073/pnas.88.11.4703 }}
* {{cite journal | vauthors = Chapman CG, Browne MJ | title = Isolation of the human ml (Hml) muscarinic acetylcholine receptor gene by PCR amplification. | journal = Nucleic Acids Res. | volume = 18 | issue = 8 | pages = 2191 | year = 1990 | pmid = 2336407 | pmc = 330717 | doi = 10.1093/nar/18.8.2191 }}
* {{cite journal | vauthors = Ashkenazi A, Ramachandran J, Capon DJ | title = Acetylcholine analogue stimulates DNA synthesis in brain-derived cells via specific muscarinic receptor subtypes. | journal = Nature | volume = 340 | issue = 6229 | pages = 146–50 | year = 1989 | pmid = 2739737 | doi = 10.1038/340146a0 }}
* {{cite journal | vauthors = Bonner TI, Buckley NJ, Young AC, Brann MR | title = Identification of a family of muscarinic acetylcholine receptor genes. | journal = Science | volume = 237 | issue = 4814 | pages = 527–32 | year = 1987 | pmid = 3037705 | doi = 10.1126/science.3037705 }}
* {{cite journal | vauthors = Peralta EG, Ashkenazi A, Winslow JW, Smith DH, Ramachandran J, Capon DJ | title = Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors. | journal = EMBO J. | volume = 6 | issue = 13 | pages = 3923–9 | year = 1988 | pmid = 3443095 | pmc = 553870 | doi =  }}
* {{cite journal | vauthors = Allard WJ, Sigal IS, Dixon RA | title = Sequence of the gene encoding the human M1 muscarinic acetylcholine receptor. | journal = Nucleic Acids Res. | volume = 15 | issue = 24 | pages = 10604 | year = 1988 | pmid = 3697105 | pmc = 339984 | doi = 10.1093/nar/15.24.10604 }}
* {{cite journal | vauthors = Svoboda P, Milligan G | title = Agonist-induced transfer of the alpha subunits of the guanine-nucleotide-binding regulatory proteins Gq and G11 and of muscarinic m1 acetylcholine receptors from plasma membranes to a light-vesicular membrane fraction. | journal = Eur. J. Biochem. | volume = 224 | issue = 2 | pages = 455–62 | year = 1994 | pmid = 7925360 | doi = 10.1111/j.1432-1033.1994.00455.x }}
* {{cite journal | vauthors = Crespo P, Xu N, Daniotti JL, Troppmair J, Rapp UR, Gutkind JS | title = Signaling through transforming G protein-coupled receptors in NIH 3T3 cells involves c-Raf activation. Evidence for a protein kinase C-independent pathway. | journal = J. Biol. Chem. | volume = 269 | issue = 33 | pages = 21103–9 | year = 1994 | pmid = 8063729 | doi =  }}
* {{cite journal | vauthors = Russell M, Winitz S, Johnson GL | title = Acetylcholine muscarinic m1 receptor regulation of cyclic AMP synthesis controls growth factor stimulation of Raf activity. | journal = Mol. Cell. Biol. | volume = 14 | issue = 4 | pages = 2343–51 | year = 1994 | pmid = 8139539 | pmc = 358601 | doi = 10.1128/mcb.14.4.2343 }}
* {{cite journal | vauthors = Offermanns S, Wieland T, Homann D, Sandmann J, Bombien E, Spicher K, Schultz G, Jakobs KH | title = Transfected muscarinic acetylcholine receptors selectively couple to Gi-type G proteins and Gq/11. | journal = Mol. Pharmacol. | volume = 45 | issue = 5 | pages = 890–8 | year = 1994 | pmid = 8190105 | doi =  }}
* {{cite journal | vauthors = Mullaney I, Mitchell FM, McCallum JF, Buckley NJ, Milligan G | title = The human muscarinic M1 acetylcholine receptor, when express in CHO cells, activates and downregulates both Gq alpha and G11 alpha equally and non-selectively. | journal = FEBS Lett. | volume = 324 | issue = 2 | pages = 241–5 | year = 1993 | pmid = 8508928 | doi = 10.1016/0014-5793(93)81401-K }}
* {{cite journal | vauthors = Courseaux A, Grosgeorge J, Gaudray P, Pannett AA, Forbes SA, Williamson C, Bassett D, Thakker RV, Teh BT, Farnebo F, Shepherd J, Skogseid B, Larsson C, Giraud S, Zhang CX, Salandre J, Calender A | title = Definition of the minimal MEN1 candidate area based on a 5-Mb integrated map of proximal 11q13. The European Consortium on Men1, (GENEM 1; Groupe d'Etude des Néoplasies Endocriniennes Multiples de type 1). | journal = Genomics | volume = 37 | issue = 3 | pages = 354–65 | year = 1997 | pmid = 8938448 | doi = 10.1006/geno.1996.0570 }}
* {{cite journal | vauthors = Ishiyama A, López I, Wackym PA | title = Molecular characterization of muscarinic receptors in the human vestibular periphery. Implications for pharmacotherapy. | journal = The American journal of otology | volume = 18 | issue = 5 | pages = 648–54 | year = 1998 | pmid = 9303164 | doi =  }}
* {{cite journal | vauthors = Ishizaka N, Noda M, Yokoyama S, Kawasaki K, Yamamoto M, Higashida H | title = Muscarinic acetylcholine receptor subtypes in the human iris. | journal = Brain Res. | volume = 787 | issue = 2 | pages = 344–7 | year = 1998 | pmid = 9518684 | doi = 10.1016/S0006-8993(97)01554-0 }}
{{Refend}}


==References==
== External links ==
{{reflist|2}}
* {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2139 | title = Acetylcholine receptors (muscarinic): M<sub>1</sub> | accessdate = | format = | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | pages = | archiveurl = | archivedate = | quote = }}
==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =  
*{{cite journal  | author=Goyal RK |title=Muscarinic receptor subtypes. Physiology and clinical implications. |journal=N. Engl. J. Med. |volume=321 |issue= 15 |pages= 1022-9 |year= 1989 |pmid= 2674717 |doi=  }}
*{{cite journal  | author=Brann MR, Ellis J, Jørgensen H, ''et al.'' |title=Muscarinic acetylcholine receptor subtypes: localization and structure/function. |journal=Prog. Brain Res. |volume=98 |issue= |pages= 121-7 |year= 1994 |pmid= 8248499 |doi=  }}
*{{cite journal  | author=Nitsch RM, Slack BE, Wurtman RJ, Growdon JH |title=Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors. |journal=Science |volume=258 |issue= 5080 |pages= 304-7 |year= 1992 |pmid= 1411529 |doi=  }}
*{{cite journal  | author=Arden JR, Nagata O, Shockley MS, ''et al.'' |title=Mutational analysis of third cytoplasmic loop domains in G-protein coupling of the HM1 muscarinic receptor. |journal=Biochem. Biophys. Res. Commun. |volume=188 |issue= 3 |pages= 1111-5 |year= 1992 |pmid= 1445347 |doi=  }}
*{{cite journal  | author=Gutkind JS, Novotny EA, Brann MR, Robbins KC |title=Muscarinic acetylcholine receptor subtypes as agonist-dependent oncogenes. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=88 |issue= 11 |pages= 4703-7 |year= 1991 |pmid= 1905013 |doi=  }}
*{{cite journal  | author=Chapman CG, Browne MJ |title=Isolation of the human ml (Hml) muscarinic acetylcholine receptor gene by PCR amplification. |journal=Nucleic Acids Res. |volume=18 |issue= 8 |pages= 2191 |year= 1990 |pmid= 2336407 |doi=  }}
*{{cite journal  | author=Ashkenazi A, Ramachandran J, Capon DJ |title=Acetylcholine analogue stimulates DNA synthesis in brain-derived cells via specific muscarinic receptor subtypes. |journal=Nature |volume=340 |issue= 6229 |pages= 146-50 |year= 1989 |pmid= 2739737 |doi= 10.1038/340146a0 }}
*{{cite journal  | author=Bonner TI, Buckley NJ, Young AC, Brann MR |title=Identification of a family of muscarinic acetylcholine receptor genes. |journal=Science |volume=237 |issue= 4814 |pages= 527-32 |year= 1987 |pmid= 3037705 |doi=  }}
*{{cite journal  | author=Peralta EG, Ashkenazi A, Winslow JW, ''et al.'' |title=Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors. |journal=EMBO J. |volume=6 |issue= 13 |pages= 3923-9 |year= 1988 |pmid= 3443095 |doi=  }}
*{{cite journal  | author=Allard WJ, Sigal IS, Dixon RA |title=Sequence of the gene encoding the human M1 muscarinic acetylcholine receptor. |journal=Nucleic Acids Res. |volume=15 |issue= 24 |pages= 10604 |year= 1988 |pmid= 3697105 |doi=  }}
*{{cite journal  | author=Svoboda P, Milligan G |title=Agonist-induced transfer of the alpha subunits of the guanine-nucleotide-binding regulatory proteins Gq and G11 and of muscarinic m1 acetylcholine receptors from plasma membranes to a light-vesicular membrane fraction. |journal=Eur. J. Biochem. |volume=224 |issue= 2 |pages= 455-62 |year= 1994 |pmid= 7925360 |doi=  }}
*{{cite journal  | author=Crespo P, Xu N, Daniotti JL, ''et al.'' |title=Signaling through transforming G protein-coupled receptors in NIH 3T3 cells involves c-Raf activation. Evidence for a protein kinase C-independent pathway. |journal=J. Biol. Chem. |volume=269 |issue= 33 |pages= 21103-9 |year= 1994 |pmid= 8063729 |doi=  }}
*{{cite journal  | author=Russell M, Winitz S, Johnson GL |title=Acetylcholine muscarinic m1 receptor regulation of cyclic AMP synthesis controls growth factor stimulation of Raf activity. |journal=Mol. Cell. Biol. |volume=14 |issue= 4 |pages= 2343-51 |year= 1994 |pmid= 8139539 |doi=  }}
*{{cite journal  | author=Offermanns S, Wieland T, Homann D, ''et al.'' |title=Transfected muscarinic acetylcholine receptors selectively couple to Gi-type G proteins and Gq/11. |journal=Mol. Pharmacol. |volume=45 |issue= 5 |pages= 890-8 |year= 1994 |pmid= 8190105 |doi=  }}
*{{cite journal  | author=Mullaney I, Mitchell FM, McCallum JF, ''et al.'' |title=The human muscarinic M1 acetylcholine receptor, when express in CHO cells, activates and downregulates both Gq alpha and G11 alpha equally and non-selectively. |journal=FEBS Lett. |volume=324 |issue= 2 |pages= 241-5 |year= 1993 |pmid= 8508928 |doi=  }}
*{{cite journal  | author=Courseaux A, Grosgeorge J, Gaudray P, ''et al.'' |title=Definition of the minimal MEN1 candidate area based on a 5-Mb integrated map of proximal 11q13. The European Consortium on Men1, (GENEM 1; Groupe d'Etude des Néoplasies Endocriniennes Multiples de type 1). |journal=Genomics |volume=37 |issue= 3 |pages= 354-65 |year= 1997 |pmid= 8938448 |doi=  }}
*{{cite journal  | author=Ishiyama A, López I, Wackym PA |title=Molecular characterization of muscarinic receptors in the human vestibular periphery. Implications for pharmacotherapy. |journal=The American journal of otology |volume=18 |issue= 5 |pages= 648-54 |year= 1998 |pmid= 9303164 |doi=  }}
*{{cite journal  | author=Ishizaka N, Noda M, Yokoyama S, ''et al.'' |title=Muscarinic acetylcholine receptor subtypes in the human iris. |journal=Brain Res. |volume=787 |issue= 2 |pages= 344-7 |year= 1998 |pmid= 9518684 |doi=  }}
}}
{{refend}}


{{NLM content}}
{{NLM content}}
{{membrane-protein-stub}}
{{G protein-coupled receptors|g1}}
{{G protein-coupled receptors}}
{{Muscarinic acetylcholine receptor modulators}}
[[Category:G protein coupled receptors]]
{{Use dmy dates|date=February 2011}}
 
{{DEFAULTSORT:Muscarinic Acetylcholine Receptor M1}}
 
[[Category:Muscarinic acetylcholine receptors]]

Revision as of 17:52, 4 December 2017

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Orthologs
SpeciesHumanMouse
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The muscarinic acetylcholine receptor M1, also known as the cholinergic receptor, muscarinic 1, is a muscarinic receptor that in humans is encoded by the CHRM1 gene.[1] It is localized to 11q13.[1]

This receptor is found mediating slow EPSP at the ganglion in the postganglionic nerve,[2] is common in exocrine glands and in the CNS.[3][4]

It is predominantly found bound to G proteins of class Gq[5][6] that use upregulation of phospholipase C and, therefore, inositol trisphosphate and intracellular calcium as a signalling pathway. A receptor so bound would not be susceptible to CTX or PTX. However, Gi (causing a downstream decrease in cAMP) and Gs (causing an increase in cAMP) have also been shown to be involved in interactions in certain tissues, and so would be susceptible to PTX and CTX respectively.

Effects

Orthologs

A structural homolog of M1 receptor is expressed in unicellular eukaryotes, such as Acanthamoeba castellanii.[10] and Naegleria fowleri.[11] The receptor antagonists of M1 receptors have shown to be exert anti-proliferative effects on these amoebae.

Mechanism

It couples to Gq, and, to a small extent, Gi and Gs. This results in slow EPSP and decreased K+ conductance.[8][12] It is preassembled to the Gq heterotrimer through a polybasic c-terminal domain.[5]

Ligands

Agonists

Allosteric modulators

Antagonists

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 "Entrez Gene: CHRM1 cholinergic receptor, muscarinic 1".
  2. ↑ Messer WS (2000-01-20). "Acetylcholine". University of Toledo. Archived from the original on 14 October 2007. Retrieved 2007-10-27.
  3. ↑ Johnson G (2002). PDQ Pharmacology (2nd ed.). Hamilton, Ontario: BC Decker Inc. pp. 311 pages. ISBN 1-55009-109-3.
  4. ↑ Richelson E (1995). "Cholinergic Transduction". In Bloom FE, Kupfer DJ. Psychopharmacology: the fourth generation of progress: an official publication of the American College of Neuropsychopharmacology (Fourth ed.). New York: Lippincott Williams & Wilkins. ISBN 978-0781701662. Retrieved 2007-10-27.
  5. ↑ 5.0 5.1 Qin K, Dong C, Wu G, Lambert NA (August 2011). "Inactive-state preassembly of Gq-coupled receptors and Gq heterotrimers". Nature Chemical Biology. 7 (11): 740–747. doi:10.1038/nchembio.642. PMC 3177959. PMID 21873996.
  6. ↑ Burford NT, Nahorski SR (1996). "Muscarinic m1 receptor-stimulated adenylate cyclase activity in Chinese hamster ovary cells is mediated by Gs alpha and is not a consequence of phosphoinositidase C activation". Biochem. J. 315 (Pt 3): 883–8. PMC 1217289. PMID 8645172.
  7. ↑ Harada K, Matsuoka H, Miyata H, Matsui M, Inoue M (Mar 2015). "Identification of muscarinic receptor subtypes involved in catecholamine secretion in adrenal medullary chromaffin cells by genetic deletion". British Journal of Pharmacology. 172 (5): 1348–59. doi:10.1111/bph.13011. PMC 4337706. PMID 25393049.
  8. ↑ 8.0 8.1 8.2 8.3 8.4 8.5 8.6 8.7 8.8 8.9 Rang HP, Dale MM, Ritter JM, Moore PK (2003). "10". Pharmacology (5th ed.). Elsevier Churchill Livingstone. p. 139. ISBN 0-443-07145-4.
  9. ↑ Smith RS, Hu R, DeSouza A, Eberly CL, Krahe K, Chan W, Araneda RC (Jul 2015). "Differential Muscarinic Modulation in the Olfactory Bulb". The Journal of Neuroscience. 35 (30): 10773–85. doi:10.1523/JNEUROSCI.0099-15.2015. PMC 4518052. PMID 26224860.
  10. ↑ Baig AM, Ahmad HR (2016). "Evidence of a M1-muscarinic GPCR homolog in unicellular eukaryotes: featuring Acanthamoeba spp bioinformatics 3D-modelling and experimentations". Journal of Receptor and Signal Transduction Research: 1–9. doi:10.1080/10799893.2016.1217884. PMID 27601178.
  11. ↑ Baig AM (2016). "Primary Amoebic Meningoencephalitis: Neurochemotaxis and Neurotropic Preferences of Naegleria fowleri". ACS Chemical Neuroscience. 7 (8): 1026–9. doi:10.1021/acschemneuro.6b00197. PMID 27447543.
  12. ↑ Uchimura N, North RA (1 March 1990). "Muscarine reduces inwardly rectifying potassium conductance in rat nucleus accumbens neurones". J. Physiol. 422 (1): 369–80. doi:10.1113/jphysiol.1990.sp017989. PMC 1190137. PMID 1693682.
  13. ↑ Hamilton SE, Loose MD, Qi M, Levey AI, Hille B, McKnight GS, Idzerda RL, Nathanson NM (1997). "Disruption of the m1 receptor gene ablates muscarinic receptor-dependent M current regulation and seizure activity in mice" (PDF). Proc. Natl. Acad. Sci. U.S.A. 94 (24): 13311–6. doi:10.1073/pnas.94.24.13311. PMC 24305. PMID 9371842.
  14. ↑ Shirey JK, Brady AE, Jones PJ, Davis AA, Bridges TM, Kennedy JP, Jadhav SB, Menon UN, Xiang Z, Watson ML, Christian EP, Doherty JJ, Quirk MC, Snyder DH, Lah JJ, Levey AI, Nicolle MM, Lindsley CW, Conn PJ (November 2009). "A selective allosteric potentiator of the M1 muscarinic acetylcholine receptor increases activity of medial prefrontal cortical neurons and restores impairments in reversal learning". J. Neurosci. 29 (45): 14271–86. doi:10.1523/JNEUROSCI.3930-09.2009. PMC 2811323. PMID 19906975.
  15. ↑ Bradley SJ, Bourgognon JM, Sanger HE, Verity N, Mogg AJ, White DJ, Butcher AJ, Moreno JA, Molloy C, Macedo-Hatch T, Edwards JM, Wess J, Pawlak R, Read DJ, Sexton PM, Broad LM, Steinert JR, Mallucci GR, Christopoulos A, Felder CC, Tobin AB (2017). "M1 muscarinic allosteric modulators slow prion neurodegeneration and restore memory loss". The Journal of Clinical Investigation. 127 (2): 487–499. doi:10.1172/JCI87526. PMC 5272187. PMID 27991860.
  16. ↑ 16.0 16.1 Marlo JE, Niswender CM, Days EL, Bridges TM, Xiang Y, Rodriguez AL, Shirey JK, Brady AE, Nalywajko T, Luo Q, Austin CA, Williams MB, Kim K, Williams R, Orton D, Brown HA, Lindsley CW, Weaver CD, Conn PJ (2008). "Discovery and characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity". Mol. Pharmacol. 75 (3): 577–88. doi:10.1124/mol.108.052886. PMC 2684909. PMID 19047481.
  17. ↑ Smith, Deborah L.; Davoren, Jennifer E.; Edgerton, Jeremy R.; Lazzaro, John T.; Lee, Che-Wah; Neal, Sarah; Zhang, Lei; Grimwood, Sarah (2016-09-01). "Characterization of a Novel M1 Muscarinic Acetylcholine Receptor Positive Allosteric Modulator Radioligand, [3H]PT-1284". Molecular Pharmacology. 90 (3): 177–187. doi:10.1124/mol.116.104737. ISSN 0026-895X. PMID 27382013.
  18. ↑ Edwards Pharmaceuticals, Inc.; Belcher Pharmaceuticals, Inc. (May 2010). "DailyMed". U.S. National Library of Medicine. Retrieved January 13, 2013.

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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