Muscarinic acetylcholine receptor M1
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 Gq[4][5] 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
- EPSP in autonomic ganglia
- Secretion of catecholamines from the adrenal medulla[6]
- Secretion from salivary glands
- Gastric acid secretion from stomach[7]
- In CNS (memory?)[8]
- Vagally-induced bronchoconstriction[7]
Mechanism
It couples to Gq, and, to a small extent, Gi and Gs. This results in slow EPSP and decreased K+ conductance[8][9] It is preassembled to the Gq heterotrimer through a polybasic c-terminal domain.[4]
Ligands
Agonists
- acetylcholine
- carbachol[8]
- CDD-0097
- Cevimeline
- McN-A-343 - mixed M1/M4 agonist[8]
- L-689,660 - mixed M1/M3 agonist
- Oxotremorine
- Vedaclidine
- Xanomeline
- Muscarine
- 77-LH-28-1 - brain penetrant selective M1 allosteric agonist
- pilocarpine[10]
Allosteric modulators
Antagonists
- atropine[8]
- Hyoscyamine[13]
- dicycloverine[8]
- tolterodine[8]
- oxybutynin[8]
- ipratropium[8]
- mamba toxin muscarinic toxin 7 (MT7)[8]
- olanzapine
- pirenzepine
- telenzepine
Gene
The receptor is encoded by human gene CHRM1.[7] It is localized to 11q13.[7]
See also
References
- ↑ Messer, Jr, WS (2000-01-20). "Acetylcholine". University of Toledo. Retrieved 2007-10-27.
- ↑ 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 2007-10-27.
- ↑ 4.0 4.1 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 3177959. PMID 21873996.
- ↑ 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.
- ↑ Harada, K; Matsuoka, H; Miyata, H; Matsui, M; Inoue, M (March 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. PMID 25393049.
- ↑ 7.0 7.1 7.2 7.3 "Entrez Gene: CHRM1 cholinergic receptor, muscarinic 1".
- ↑ 8.0 8.1 8.2 8.3 8.4 8.5 8.6 8.7 8.8 8.9 Rang HP, Dale MM, Ritter JM, Moore PK (2003). "10". Pharmacology (5th ed.). Elsevier Churchill Livingstone. p. 139. ISBN 0-443-07145-4.
- ↑ 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 1190137. PMID 1693682.
- ↑ http://www.pnas.org/content/94/24/13311.full.pdf
- ↑ Shirey JK, Brady AE, Jones PJ, Davis AA, Bridges TM, Kennedy JP et al. (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.
- ↑ 12.0 12.1 Marlo JE, Niswender CM, Days EL, Bridges TM, Xiang Y, Rodriguez AL 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.
- ↑ Edwards Pharmaceuticals, Inc.; Belcher Pharmaceuticals, Inc. (May 2010), DailyMed, U.S. National Library of Medicine, retrieved January 13, 2013
Further reading
- Goyal RK (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, Hill-Eubanks D, Jones SV (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, Philip M, Lameh J, Sadée W (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.
- 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.
- 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, Smith DH, Ramachandran J, Capon DJ (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.
- 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.
- 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, Troppmair J, Rapp UR, Gutkind JS (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. doi:10.1128/mcb.14.4.2343. PMC 358601. PMID 8139539.
- Offermanns S, Wieland T, Homann D, Sandmann J, Bombien E, Spicher K 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, Buckley NJ, Milligan G (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, Pannett AA, Forbes SA, Williamson C 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. doi:10.1006/geno.1996.0570. 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, Kawasaki K, Yamamoto M, Higashida H (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.
External links
- "Acetylcholine receptors (muscarinic): M1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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