Muscarinic acetylcholine receptor M1

CHRM1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCHRM1, HM1, M1, M1R, cholinergic receptor muscarinic 1
External IDsMGI: 88396 HomoloGene: 20189 GeneCards: CHRM1
Gene location (Human)
Chr.Chromosome 11 (human)[1]
Band11q12.3Start62,908,679 bp[1]
End62,921,807 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

1128

12669

Ensembl

ENSG00000168539

ENSMUSG00000032773

UniProt

P11229

P12657

RefSeq (mRNA)

NM_000738

NM_001112697
NM_007698

RefSeq (protein)

NP_000729

NP_001106167
NP_031724

Location (UCSC)Chr 11: 62.91 – 62.92 MbChr 19: 8.66 – 8.68 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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.[5] It is localized to 11q13.[5]

This receptor is found mediating slow EPSP at the ganglion in the postganglionic nerve,[6] is common in exocrine glands and in the CNS.[7][8]

It is predominantly found bound to G proteins of class Gq[9][10] 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.[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 Gq, and, to a small extent, Gi and Gs. This results in slow EPSP and decreased K+ conductance.[11][15] It is preassembled to the Gq heterotrimer through a polybasic c-terminal domain.[9]

Ligands

Agonists

Allosteric modulators

  • benzylquinolone carboxylic acid[17]
  • BQZ-12[18]
  • VU-0090157[19]
  • VU-0029767[19]
  • [3H]PT-1284- M1-selective PAM Radioligand[20]

Antagonists

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000168539 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000032773 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:".
  4. ↑ "Mouse PubMed Reference:".
  5. 1 2 3 4 "Entrez Gene: CHRM1 cholinergic receptor, muscarinic 1".
  6. ↑ Messer WS (2000-01-20). "Acetylcholine". University of Toledo. Archived from the original on 14 October 2007. Retrieved 2007-10-27.
  7. ↑ Johnson G (2002). PDQ Pharmacology (2nd ed.). Hamilton, Ontario: BC Decker Inc. pp. 311 pages. ISBN 1-55009-109-3.
  8. ↑ 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.
  9. 1 2 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.
  10. ↑ 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.
  11. 1 2 3 4 5 6 7 8 9 10 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 (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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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.
  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". The Journal of Neuroscience. 29 (45): 14271–86. doi:10.1523/JNEUROSCI.3930-09.2009. PMC 2811323. PMID 19906975.
  18. ↑ 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.
  19. 1 2 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.
  20. ↑ 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.
  21. ↑ Edwards Pharmaceuticals, Inc.; Belcher Pharmaceuticals, Inc. (May 2010). "DailyMed". U.S. National Library of Medicine. Retrieved January 13, 2013.
  22. ↑ 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

  • Goyal RK (October 1989). "Muscarinic receptor subtypes. Physiology and clinical implications". The New England Journal of Medicine. 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". Progress in Brain Research. 98: 121–7. doi:10.1016/S0079-6123(08)62388-2. PMID 8248499.
  • Nitsch RM, Slack BE, Wurtman RJ, Growdon JH (October 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 (November 1992). "Mutational analysis of third cytoplasmic loop domains in G-protein coupling of the HM1 muscarinic receptor". Biochemical and Biophysical Research Communications. 188 (3): 1111–5. doi:10.1016/0006-291X(92)91346-R. PMID 1445347.
  • Gutkind JS, Novotny EA, Brann MR, Robbins KC (June 1991). "Muscarinic acetylcholine receptor subtypes as agonist-dependent oncogenes". Proceedings of the National Academy of Sciences of the United States of America. 88 (11): 4703–7. doi:10.1073/pnas.88.11.4703. PMC 51734. PMID 1905013.
  • Chapman CG, Browne MJ (April 1990). "Isolation of the human ml (Hml) muscarinic acetylcholine receptor gene by PCR amplification". Nucleic Acids Research. 18 (8): 2191. doi:10.1093/nar/18.8.2191. PMC 330717. PMID 2336407.
  • Ashkenazi A, Ramachandran J, Capon DJ (July 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 (July 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 (December 1987). "Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors". The EMBO Journal. 6 (13): 3923–9. PMC 553870. PMID 3443095.
  • Allard WJ, Sigal IS, Dixon RA (December 1987). "Sequence of the gene encoding the human M1 muscarinic acetylcholine receptor". Nucleic Acids Research. 15 (24): 10604. doi:10.1093/nar/15.24.10604. PMC 339984. PMID 3697105.
  • Svoboda P, Milligan G (September 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". European Journal of Biochemistry. 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 (August 1994). "Signaling through transforming G protein-coupled receptors in NIH 3T3 cells involves c-Raf activation. Evidence for a protein kinase C-independent pathway". The Journal of Biological Chemistry. 269 (33): 21103–9. PMID 8063729.
  • Russell M, Winitz S, Johnson GL (April 1994). "Acetylcholine muscarinic m1 receptor regulation of cyclic AMP synthesis controls growth factor stimulation of Raf activity". Molecular and Cellular Biology. 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 (May 1994). "Transfected muscarinic acetylcholine receptors selectively couple to Gi-type G proteins and Gq/11". Molecular Pharmacology. 45 (5): 890–8. PMID 8190105.
  • Mullaney I, Mitchell FM, McCallum JF, Buckley NJ, Milligan G (June 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 Letters. 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 (November 1996). "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 (September 1997). "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 (March 1998). "Muscarinic acetylcholine receptor subtypes in the human iris". Brain Research. 787 (2): 344–7. doi:10.1016/S0006-8993(97)01554-0. PMID 9518684.
  • "Acetylcholine receptors (muscarinic): M1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.

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