Muscarinic acetylcholine receptor M1

CHRM1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5CXV
Identifiers
Aliases	CHRM1, HM1, M1, M1R, cholinergic receptor muscarinic 1
External IDs	MGI: 88396 HomoloGene: 20189 GeneCards: CHRM1
Targeted by Drug
acetylcholine, arecoline, bethanechol, milameline, pilocarpine, sabcomeline, xanomeline, brucine, vinburnine, vincamine, clozapine, norclozapine, staurosporine, aclidinium, AFDX384, amitriptyline, biperiden, darifenacin, dicyclomine, glycopyrrolate, himbacine, methoctramine free base, oxybutynin, pirenzepine, propantheline, 3-quinuclidinyl-benzilate, tolterodine, trihexyphenidyl, umeclidinium, oxotremorine[1]
Gene ontology Molecular function • G-protein coupled receptor activity • signal transducer activity • drug binding • G-protein coupled acetylcholine receptor activity • phosphatidylinositol phospholipase C activity Cellular component • axon terminus • integral component of membrane • postsynaptic membrane • membrane • postsynaptic density • plasma membrane • integral component of plasma membrane • cell junction • dendrite • asymmetric synapse • synapse Biological process • positive regulation of intracellular protein transport • G-protein coupled receptor signaling pathway • cognition • regulation of locomotion • synaptic transmission, cholinergic • saliva secretion • nervous system development • neuromuscular synaptic transmission • protein kinase C-activating G-protein coupled receptor signaling pathway • cellular protein modification process • adenylate cyclase-inhibiting G-protein coupled acetylcholine receptor signaling pathway • positive regulation of ion transport • positive regulation of cell proliferation • phospholipase C-activating G-protein coupled acetylcholine receptor signaling pathway • cell proliferation • regulation of vascular smooth muscle contraction • signal transduction • G-protein coupled acetylcholine receptor signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	1128	12669
Ensembl	ENSG00000168539	ENSMUSG00000032773
UniProt	P11229	P12657
RefSeq (mRNA)	NM_000738	NM_001112697 NM_007698
RefSeq (protein)	NP_000729.2	NP_001106167.1 NP_031724.2
Location (UCSC)	Chr 11: 62.91 – 62.92 Mb	Chr 19: 8.66 – 8.68 Mb
PubMed search	[2]	[3]
Wikidata

View/Edit Human

View/Edit Mouse

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.^[4] It is localized to 11q13.^[4]

This receptor is found mediating slow EPSP at the ganglion in the postganglionic nerve,^[5] is common in exocrine glands and in the CNS.^[6][7]

It is predominantly found bound to G proteins of class G_q^[8][9] 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, G_i (causing a downstream decrease in cAMP) and G_s (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

• EPSP in autonomic ganglia
• Secretion of catecholamines from the adrenal medulla^[10]
• Secretion from salivary glands
• Gastric acid secretion from stomach^[4]
• In CNS (memory?)^[11]
• Vagally-induced bronchoconstriction^[4]
• Mediating olfactory behaviors (e.g. aggression, mating) ^[12]

Orthologs

A structural homolog of M1 receptor is expressed in unicellular eukaryotes, such as Acanthamoeba castellanii.^[13] and Naegleria fowleri.^[14] The receptor antagonists of M1 receptors have shown to be exert anti-proliferative effects on these amoebae.

Mechanism

It couples to G_q, and, to a small extent, G_i and G_s. This results in slow EPSP and decreased K⁺ conductance^[11][15] It is preassembled to the Gq heterotrimer through a polybasic c-terminal domain.^[8]

Ligands

Agonists

• acetylcholine
• carbachol^[11]
• cevimeline
• muscarine
• oxotremorine
• pilocarpine^[16]
• vedaclidine
• xanomeline
• 77-LH-28-1 - brain penetrant selective M₁ allosteric agonist
• CDD-0097
• McN-A-343 - mixed M1/M4 agonist^[11]
• L-689,660 - mixed M1/M3 agonist

Allosteric modulators

• benzylquinolone carboxylic acid^[17]
• VU-0090157^[18]
• VU-0029767^[18]

Antagonists

• atropine^[11]
• dicycloverine^[11]
• hyoscyamine^[19]
• ipratropium^[11]
• mamba toxin muscarinic toxin 7 (MT7)^[11]
• olanzapine
• oxybutynin^[11]
• pirenzepine
• telenzepine
• tolterodine^[11]

See also

• Muscarinic acetylcholine receptor

References

1. "Drugs that physically interact with Muscarinic acetylcholine receptor M1 view/edit references on wikidata".
2. "Human PubMed Reference:".
3. "Mouse PubMed Reference:".
4. "Entrez Gene: CHRM1 cholinergic receptor, muscarinic 1".
5. Messer WS (2000-01-20). "Acetylcholine". University of Toledo. Archived from the original on 14 October 2007. Retrieved 2007-10-27.
6. Johnson G (2002). PDQ Pharmacology (2nd ed.). Hamilton, Ontario: BC Decker Inc. pp. 311 pages. ISBN 1-55009-109-3.
7. 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.
8. 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.
9. 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.
10. 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. PMID 25393049.
11. Rang HP, Dale MM, Ritter JM, Moore PK (2003). "10". Pharmacology (5th ed.). Elsevier Churchill Livingstone. p. 139. ISBN 0-443-07145-4.
12. 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. PMID 26224860.
13. 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.
14. 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.
15. Uchimura N, North RA (1 March 1990). "Muscarine reduces inwardly rectifying potassium conductance in rat nucleus accumbens neurones". J. Physiol. (Lond.). 422 (1): 369–80. doi:10.1113/jphysiol.1990.sp017989. PMC 1190137. PMID 1693682.
16. 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.
17. 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.
18. 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.
19. Edwards Pharmaceuticals, Inc.; Belcher Pharmaceuticals, Inc. (May 2010). "DailyMed". U.S. National Library of Medicine. Retrieved January 13, 2013.

Further reading

• Goyal RK (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, Hill-Eubanks D, Jones SV (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.
• Nitsch RM, Slack BE, Wurtman RJ, Growdon JH (1992). "Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors.". Science. 258 (5080): 304–7. doi:10.1126/science.1411529. PMID 1411529.
• Arden JR, Nagata O, Shockley MS, Philip M, Lameh J, Sadée W (1992). "Mutational analysis of third cytoplasmic loop domains in G-protein coupling of the HM1 muscarinic receptor.". Biochem. Biophys. Res. Commun. 188 (3): 1111–5. doi:10.1016/0006-291X(92)91346-R. PMID 1445347.
• Gutkind JS, Novotny EA, Brann MR, Robbins KC (1991). "Muscarinic acetylcholine receptor subtypes as agonist-dependent oncogenes.". Proc. Natl. Acad. Sci. U.S.A. 88 (11): 4703–7. doi:10.1073/pnas.88.11.4703. PMC 51734. PMID 1905013.
• Chapman CG, Browne MJ (1990). "Isolation of the human ml (Hml) muscarinic acetylcholine receptor gene by PCR amplification.". Nucleic Acids Res. 18 (8): 2191. doi:10.1093/nar/18.8.2191. PMC 330717. PMID 2336407.
• 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.
• 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. PMC 553870. PMID 3443095.
• Allard WJ, Sigal IS, Dixon RA (1988). "Sequence of the gene encoding the human M1 muscarinic acetylcholine receptor.". Nucleic Acids Res. 15 (24): 10604. doi:10.1093/nar/15.24.10604. PMC 339984. PMID 3697105.
• Svoboda P, Milligan G (1994). "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.". Eur. J. Biochem. 224 (2): 455–62. doi:10.1111/j.1432-1033.1994.00455.x. PMID 7925360.
• Crespo P, Xu N, Daniotti JL, Troppmair J, Rapp UR, Gutkind JS (1994). "Signaling through transforming G protein-coupled receptors in NIH 3T3 cells involves c-Raf activation. Evidence for a protein kinase C-independent pathway.". J. Biol. Chem. 269 (33): 21103–9. PMID 8063729.
• Russell M, Winitz S, Johnson GL (1994). "Acetylcholine muscarinic m1 receptor regulation of cyclic AMP synthesis controls growth factor stimulation of Raf activity.". Mol. Cell. Biol. 14 (4): 2343–51. doi:10.1128/mcb.14.4.2343. PMC 358601. PMID 8139539.
• Offermanns S, Wieland T, Homann D, Sandmann J, Bombien E, Spicher K, Schultz G, Jakobs KH (1994). "Transfected muscarinic acetylcholine receptors selectively couple to Gi-type G proteins and Gq/11.". Mol. Pharmacol. 45 (5): 890–8. PMID 8190105.
• Mullaney I, Mitchell FM, McCallum JF, Buckley NJ, Milligan G (1993). "The human muscarinic M1 acetylcholine receptor, when express in CHO cells, activates and downregulates both Gq alpha and G11 alpha equally and non-selectively.". FEBS Lett. 324 (2): 241–5. doi:10.1016/0014-5793(93)81401-K. PMID 8508928.
• 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 (1997). "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).". Genomics. 37 (3): 354–65. doi:10.1006/geno.1996.0570. PMID 8938448.
• Ishiyama A, López I, Wackym PA (1998). "Molecular characterization of muscarinic receptors in the human vestibular periphery. Implications for pharmacotherapy.". The American journal of otology. 18 (5): 648–54. PMID 9303164.
• Ishizaka N, Noda M, Yokoyama S, Kawasaki K, Yamamoto M, Higashida H (1998). "Muscarinic acetylcholine receptor subtypes in the human iris.". Brain Res. 787 (2): 344–7. doi:10.1016/S0006-8993(97)01554-0. PMID 9518684.

External links

• "Acetylcholine receptors (muscarinic): M₁". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.

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