Muscarinic acetylcholine receptor M₁

Template:PBB 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^{[citation needed]}, is common in exocrine glands and in the CNS.^[1]^[2]

It is predominantly found bound to G proteins of class G_q^[3]^[4] 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^{[citation needed]}
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 decreased K⁺ conductance^[6]^[7] It is preassembled to the Gq heterotrimer through a polybasic c-terminal domain.^[3]

Ligands

Agonists

acetylcholine
carbachol^[6]
CDD-0097
Cevimeline
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]
Hyoscyamine^[10]
dicycloverine^[6]
tolterodine^[6]
oxybutynin^[6]
ipratropium^[6]
mamba toxin muscarinic toxin 7 (MT7)^[6]
olanzapine
pirenzepine
telenzepine

Gene

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

References

^ Johnson, Gordon (2002). PDQ Pharmacology (2nd ed.). Hamilton, Ontario: BC Decker Inc. pp. 311 pages. ISBN 1-55009-109-3.
^ Richelson, Elliott (2000). "Cholinergic Transduction, Psychopharmacology - The Fourth Generation of Progress". American College of Neuropsychopharmacology. Retrieved 27 October 2007.
^ ^a ^b Kou Qin, Chunmin Dong, Guangyu Wu & Nevin A Lambert (August 2011). "Inactive-state preassembly of Gq-coupled receptors and Gq heterotrimers". Nature Chemical Biology. 7 (11): 740–747. doi:10.1038/nchembio.642. PMID 21873996.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ 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.
^ ^a ^b ^c ^d "Entrez Gene: CHRM1 cholinergic receptor, muscarinic 1".
^ ^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.{{cite book}}: CS1 maint: multiple names: authors list (link)
^ 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.
^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ ^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): 577–88. doi:10.1124/mol.108.052886. PMC 2684909. PMID 19047481. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
^ Edwards Pharmaceuticals, Inc.; Belcher Pharmaceuticals, Inc. (May 2010), DailyMed, U.S. National Library of Medicine, retrieved 13 January 2013{{citation}}: CS1 maint: date and year (link)

External links

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

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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)

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[isbn1-55009-109-3-1] Johnson, Gordon (2002). PDQ Pharmacology (2nd ed.). Hamilton, Ontario: BC Decker Inc. pp. 311 pages. ISBN 1-55009-109-3.

[Richelson_2000-2] Richelson, Elliott (2000). "Cholinergic Transduction, Psychopharmacology - The Fourth Generation of Progress". American College of Neuropsychopharmacology. Retrieved 27 October 2007.

[Kou_Qin-3] Kou Qin, Chunmin Dong, Guangyu Wu & Nevin A Lambert (August 2011). "Inactive-state preassembly of Gq-coupled receptors and Gq heterotrimers". Nature Chemical Biology. 7 (11): 740–747. doi:10.1038/nchembio.642. PMID 21873996.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[pmid8645172-4] 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.

[entrez-5] "Entrez Gene: CHRM1 cholinergic receptor, muscarinic 1".

[Rang-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.{{cite book}}: CS1 maint: multiple names: authors list (link)

[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.

[pmid19906975-8] 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[pmid19047481-9] 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): 577–88. doi:10.1124/mol.108.052886. PMC 2684909. PMID 19047481. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)

[10] Edwards Pharmaceuticals, Inc.; Belcher Pharmaceuticals, Inc. (May 2010), DailyMed, U.S. National Library of Medicine, retrieved 13 January 2013{{citation}}: CS1 maint: date and year (link)

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