Muscarinic acetylcholine receptor M1

Cholinergic receptor, muscarinic 1
Identifiers
Symbols	CHRM1; HM1; M1; M1R; MGC30125
External IDs	OMIM: 118510 MGI: 88396 HomoloGene: 20189 GeneCards: CHRM1 Gene
Gene Ontology Molecular function • phosphatidylinositol phospholipase C activity • receptor activity • G-protein coupled receptor activity • muscarinic acetylcholine receptor activity • protein binding • drug binding Cellular component • membrane fraction • plasma membrane • plasma membrane • integral to plasma membrane • postsynaptic density • cell junction • dendrite • asymmetric synapse • axon terminus • postsynaptic membrane Biological process • protein modification process • signal transduction • G-protein coupled receptor protein signaling pathway • activation of protein kinase C activity by G-protein coupled receptor protein signaling pathway • activation of phospholipase C activity by muscarinic acetylcholine receptor signaling pathway • muscarinic acetylcholine receptor signaling pathway • neuromuscular synaptic transmission • nervous system development • cell proliferation • positive regulation of cell proliferation • regulation of locomotion Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	1128	12669
Ensembl	ENSG00000168539	ENSMUSG00000032773
UniProt	P11229	Q52KQ0
RefSeq (mRNA)	NM_000738	NM_007698
RefSeq (protein)	NP_000729	NP_031724
Location (UCSC)	Chr 11: 62.68 – 62.69 Mb	Chr 19: 8.74 – 8.76 Mb
PubMed search	[1]	[2]

The muscarinic acetylcholine receptor M₁, also known as the cholinergic receptor, muscarinic 1, is a muscarinic receptor.

This receptor is found mediating slow EPSP at the ganglion in the postganglionic nerve,^[1] is common in exocrine glands and in the CNS.^[2][3]

It is predominantly found bound to G proteins of class G_q^[4] 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_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 from salivary glands
• gastric acid secretion from stomach^[5]
• In CNS (memory?)^[6]
• vagally-induced bronchoconstriction^[5]

Mechanism

It couples to G_q, and, to a small extent, G_i and G_s. This results in slow EPSP and decreasedK⁺ conductance^[6][7]

Ligands

Agonists

• acetylcholine
• carbachol^[6]
• CDD-0097
• McN-A-343 - mixed M1/M4 agonist^[6]
• L-689,660 - mixed M1/M3 agonist
• Oxotremorine
• Vedaclidine
• Xanomeline
• Muscarine
• 77-LH-28-1 - brain penetrant selective M₁ allosteric agonist

Allosteric modulators

• benzylquinolone carboxylic acid^[8]
• VU-0090157^[9]
• VU-0029767^[9]

Antagonists

• atropine^[6]
• dicycloverine^[6]
• tolterodine^[6]
• oxybutynin^[6]
• ipratropium^[6]
• mamba toxin muscarinic toxin 7 (MT7)^[6]
• pirenzepine
• telenzepine

Gene

The receptor is encoded by human gene CHRM1.^[5] It is localized to 11q13.^[5]

See also

• Muscarinic acetylcholine receptor

References

1. ^ Messer, Jr, WS (2000-01-20). "Acetylcholine". University of Toledo. http://www.neurosci.pharm.utoledo.edu/MBC3320/acetylcholine.htm. Retrieved 2007-10-27. 
2. ^ Johnson, Gordon (2002). PDQ Pharmacology (2nd ed.). Hamilton, Ontario: BC Decker Inc. pp. 311 pages. ISBN 1-55009-109-3. 
3. ^ Richelson, Elliott (2000). "Cholinergic Transduction, Psychopharmacology - The Fourth Generation of Progress". American College of Neuropsychopharmacology. http://www.acnp.org/g4/GN401000011/Default.htm. Retrieved 2007-10-27. 
4. ^ 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. http://www.biochemj.org/bj/315/bj3150883.htm. 
5. ^ ^{a b c d} "Entrez Gene: CHRM1 cholinergic receptor, muscarinic 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1128. 
6. ^ ^{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. 
7. ^ 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. PMC 1190137. PMID 1693682. http://www.jphysiol.org/cgi/pmidlookup?view=long&pmid=1693682. 
8. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2811323. 
9. ^ ^{a b} Marlo JE, Niswender CM, Days EL, et al. (2008). "Discovery and characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity". Mol. Pharmacol. 75 (3): 577. doi:10.1124/mol.108.052886. PMC 2684909. PMID 19047481. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2684909. 

External links

• "Acetylcholine receptors (muscarinic): M₁". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2139. 

Further reading

• Goyal RK; Underhill, Lisa H.; Goyal, Raj K. (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, et al. (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, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=51734. 
• 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=330717. 
• 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, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=553870. 
• 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=339984. 
• 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, et al. (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. PMC 358601. PMID 8139539. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=358601. 
• Offermanns S, Wieland T, Homann D, et al. (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, et al. (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, et al. (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. 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, et al. (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. 

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

This transmembrane receptor-related article is a stub. You can help Wikipedia by expanding it.v · Categories: Human proteins G protein coupled receptors Transmembrane receptor stubs Wikimedia Foundation. 2010. Игры ⚽ Поможем сделать НИР Charles-André Doudin 2007 European Racquetball Championships Look at other dictionaries: Muscarinic acetylcholine receptor — Amanita muscaria, the mushroom from which muscarine was isolated …   Wikipedia Muscarinic acetylcholine receptor M4 — Cholinergic receptor, muscarinic 4 Identifiers Symbols CHRM4; HM4; M4R External IDs …   Wikipedia Muscarinic acetylcholine receptor M2 — Cholinergic receptor, muscarinic 2 Identifiers Symbols CHRM2; FLJ43243; HM2; MGC120006; MGC120007 External IDs …   Wikipedia Muscarinic acetylcholine receptor M3 — Cholinergic receptor, muscarinic 3 Identifiers Symbols CHRM3; HM3 External IDs OMIM …   Wikipedia Muscarinic acetylcholine receptor M5 — Cholinergic receptor, muscarinic 5 Identifiers Symbols CHRM5; HM5; MGC41838 External IDs …   Wikipedia muscarinic acetylcholine receptor — Distinct from the nicotinic acetylcholine receptor in having no intrinsic ion channel; a seven membrane spanning G protein coupled receptor …   Dictionary of molecular biology Acetylcholine receptor — Acetylcholine An acetylcholine receptor (abbreviated AChR) is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter. Contents …   Wikipedia acetylcholine receptor — See nicotinic acetylcholine receptor, muscarinic acetylcholine receptor …   Dictionary of molecular biology Nicotinic acetylcholine receptor — Acetylcholine Nicotine …   Wikipedia Receptor muscarínico M3 — Saltar a navegación, búsqueda Para otros usos de este término, véase M3. Receptor muscarínico M3 Identificadores Símbolo CHRM3 Entrez …   Wikipedia Español 18+ © Academic, 2000-2024 Contact us: Technical Support, Advertising Dictionaries export, created on PHP, Joomla, Drupal, WordPress, MODx. Mark and share Search through all dictionaries Translate… Search Internet Share the article and excerpts Direct link … Do a right-click on the link above and select “Copy Link”