Muscarinic acetylcholine receptor M1

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
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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

In search of evolutionary origins of cholinergic system and muscarinic receptors in eukaryotes, a structural homolog of M1 receptor has been reported in Acanthamoeba castellanii.[9] and Naegleria fowleri.[10] 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.[7][11] 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 G(q)-coupled receptors and G(q) heterotrimers". Nature Chemical Biology. 7 (10): 740–7. doi:10.1038/nchembio.642. PMC 3177959. PMID 21873996.
  6. Burford NT, Nahorski SR (May 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". The Biochemical Journal. 315 ( Pt 3) (Pt 3): 883–8. PMC 1217289. PMID 8645172.
  7. 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 7.9 Rang HP, Dale MM, Ritter JM, Moore PK (2003). "10". Pharmacology (5th ed.). Elsevier Churchill Livingstone. p. 139. ISBN 0-443-07145-4.
  8. Smith RS, Hu R, DeSouza A, Eberly CL, Krahe K, Chan W, Araneda RC (July 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.
  9. Baig AM, Ahmad HR (June 2017). "M1-muscarinic GPCR homolog in unicellular eukaryotes: featuring Acanthamoeba spp bioinformatics 3D-modelling and experimentations". Journal of Receptor and Signal Transduction Research. 37 (3): 267–275. doi:10.1080/10799893.2016.1217884. PMID 27601178.
  10. Baig AM (August 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.
  11. Uchimura N, North RA (March 1990). "Muscarine reduces inwardly rectifying potassium conductance in rat nucleus accumbens neurones". The Journal of Physiology. 422 (1): 369–80. doi:10.1113/jphysiol.1990.sp017989. PMC 1190137. PMID 1693682.
  12. Hamilton SE, Loose MD, Qi M, Levey AI, Hille B, McKnight GS, Idzerda RL, Nathanson NM (November 1997). "Disruption of the m1 receptor gene ablates muscarinic receptor-dependent M current regulation and seizure activity in mice" (PDF). Proceedings of the National Academy of Sciences of the United States of America. 94 (24): 13311–6. doi:10.1073/pnas.94.24.13311. PMC 24305. PMID 9371842.
  13. 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". The Journal of Neuroscience. 29 (45): 14271–86. doi:10.1523/JNEUROSCI.3930-09.2009. PMC 2811323. PMID 19906975.
  14. 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 (February 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.
  15. 15.0 15.1 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 (March 2009). "Discovery and characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity". Molecular Pharmacology. 75 (3): 577–88. doi:10.1124/mol.108.052886. PMC 2684909. PMID 19047481.
  16. Smith DL, Davoren JE, Edgerton JR, Lazzaro JT, Lee CW, Neal S, Zhang L, Grimwood S (September 2016). "Characterization of a Novel M1 Muscarinic Acetylcholine Receptor Positive Allosteric Modulator Radioligand, [3H]PT-1284". Molecular Pharmacology. 90 (3): 177–87. doi:10.1124/mol.116.104737. PMID 27382013.
  17. Edwards Pharmaceuticals, Inc.; Belcher Pharmaceuticals, Inc. (May 2010). "DailyMed". U.S. National Library of Medicine. Retrieved January 13, 2013.
  18. Eltze M, Figala V (December 1988). "Affinity and selectivity of biperiden enantiomers for muscarinic receptor subtypes". European Journal of Pharmacology. 158 (1–2): 11–9. PMID 3220113.

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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