Muscarinic acetylcholine receptor M1

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CHRM1
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases CHRM1, HM1, M1, M1R, cholinergic receptor muscarinic 1
External IDs MGI: 88396 HomoloGene: 20189 GeneCards: CHRM1
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000738

NM_001112697
NM_007698

RefSeq (protein)

NP_000729

NP_001106167.1
NP_031724.2
NP_001106167
NP_031724

Location (UCSC) Chr 11: 62.91 – 62.92 Mb Chr 19: 8.66 – 8.68 Mb
PubMed search [1] [2]
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.[3] It is localized to 11q13.[3]

This receptor is found mediating slow EPSP at the ganglion in the postganglionic nerve,[4] is common in exocrine glands and in the CNS.[5][6]

It is predominantly found bound to G proteins of class Gq[7][8] 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[edit]

Orthologs[edit]

A structural homolog of M1 receptor is expressed in unicellular eukaryotes, such as Acanthamoeba castellanii.[12] and Naegleria fowleri.[13] The receptor antagonists of M1 receptors have shown to be exert anti-proliferative effects on these amoebae.

Mechanism[edit]

It couples to Gq, and, to a small extent, Gi and Gs. This results in slow EPSP and decreased K+ conductance.[10][14] It is preassembled to the Gq heterotrimer through a polybasic c-terminal domain.[7]

Ligands[edit]

Agonists[edit]

Allosteric modulators[edit]

Antagonists[edit]

See also[edit]

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ a b c d "Entrez Gene: CHRM1 cholinergic receptor, muscarinic 1". 
  4. ^ Messer WS (2000-01-20). "Acetylcholine". University of Toledo. Archived from the original on 14 October 2007. Retrieved 2007-10-27. 
  5. ^ Johnson G (2002). PDQ Pharmacology (2nd ed.). Hamilton, Ontario: BC Decker Inc. pp. 311 pages. ISBN 1-55009-109-3. 
  6. ^ 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. 
  7. ^ a b 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 3177959Freely accessible. PMID 21873996. 
  8. ^ 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 1217289Freely accessible. PMID 8645172. 
  9. ^ 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 4337706Freely accessible. PMID 25393049. 
  10. ^ a b c d e f g h i j Rang HP, Dale MM, Ritter JM, Moore PK (2003). "10". Pharmacology (5th ed.). Elsevier Churchill Livingstone. p. 139. ISBN 0-443-07145-4. 
  11. ^ 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 4518052Freely accessible. PMID 26224860. 
  12. ^ 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. 
  13. ^ 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. 
  14. ^ 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 1190137Freely accessible. PMID 1693682. 
  15. ^ 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 24305Freely accessible. PMID 9371842. 
  16. ^ 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 2811323Freely accessible. PMID 19906975. 
  17. ^ 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 5272187Freely accessible. PMID 27991860. 
  18. ^ a b 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 2684909Freely accessible. PMID 19047481. 
  19. ^ Edwards Pharmaceuticals, Inc.; Belcher Pharmaceuticals, Inc. (May 2010). "DailyMed". U.S. National Library of Medicine. Retrieved January 13, 2013. 

Further reading[edit]

External links[edit]

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