Muscarinic acetylcholine receptor M1
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| Location (UCSC) | Chr 11: 62.91 – 62.92 Mb | Chr 19: 8.64 – 8.66 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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The muscarinic acetylcholine receptor M1, also known as the cholinergic receptor, muscarinic 1, is a
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
- autonomic ganglia[citation needed]
- Secretion from salivary glands
- Gastric acid secretion from stomach[5]
- Via the
- Cognitive flexibility
- Synaptic plasticity modulation
- Anxiety-like behavior and spontaneous working memory
- Salivation
- Task switching
- Vagally-induced bronchoconstriction[5]
- Mediating olfactory behaviors and detection of "social odors" which have implications (for rodents) in aggression, mating, and social behavior.[14]
Occurrence in free living amoebae
A structural but not sequential
homolog of the human M1 receptor has been reported in Acanthamoeba castellanii[15] and Naegleria fowleri.[16] Antagonists of human M1 receptors (e.g. atropine, diphenhydramine
) have been shown to exert anti-proliferative effects on these pathogens.
Mechanism
It couples to Gq, and, to a small extent, Gi and Gs. This results in slow EPSP and decreased K+ conductance.[12][17] It is preassembled to the Gq heterotrimer through a polybasic c-terminal domain.[9]
Ligands
Agonists
- acetylcholine
- carbachol[12]
- cevimeline
- muscarine
- oxotremorine
- pilocarpine[18]
- vedaclidine
- xanomeline
- 77-LH-28-1 - brain penetrant selective M1 allosteric agonist
- CDD-0097
- McN-A-343 - mixed M1/M4 agonist[12]
- L-689, L-660 - mixed M1/M3 agonist
Allosteric modulators
- benzylquinolone carboxylic acid[19]
- BQZ-12[20]
- VU-0090157[21]
- VU-0029767[21]
- VU0467319[22]
- [3H]PT-1284- M1-selective PAM Radioligand[23]
Antagonists
- atropine[12]
- diphenhydramine
- scopolamine[24]
- tramadol[25]
- dicycloverine[12]
- fluoxetine
- hyoscyamine[26]
- ipratropium[12]
- mamba toxin muscarinic toxin 7 (MT7)[12]
- Many antipsychotics like olanzapine, quetiapine, clozapine, chlorpromazine
- pirenzepine
- oxybutynin[12]
- Benzatropine
- telenzepine
- paroxetine
- Tricyclic and tetracyclic antidepressants like clomipramine, imipramine, mirtazapine, amitriptyline
- tolterodine[12]
- Biperiden[27]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000168539 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032773 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b c d "Entrez Gene: CHRM1 cholinergic receptor, muscarinic 1".
- ^ Messer WS (20 January 2000). "Acetylcholine". University of Toledo. Archived from the original on 14 October 2007. Retrieved 27 October 2007.
- ISBN 1-55009-109-3.
- ISBN 978-0781701662. Retrieved 27 October 2007.
- ^ PMID 21873996.
- PMID 8645172.
- PMID 26589572.
Delirium is only associated with the antagonism of post‐synaptic M1 receptors and to date other receptor subtypes have not been implicated
- ^ ISBN 0-443-07145-4.
- PMID 26589572.
Delirium is only associated with the antagonism of post‐synaptic M1 receptors and to date other receptor subtypes have not been implicated
- PMID 26224860.
- S2CID 5234123.
- PMID 27447543.
- PMID 1693682.[permanent dead link]
- PMID 9371842.
- PMID 19906975.
- PMID 27991860.
- ^ PMID 19047481.
- ^ Clinical trial number NCT04051801 for "Multiple Ascending Dose Phase I Study of the M1 Positive Allosteric Modulator VU0467319" at ClinicalTrials.gov
- PMID 27382013.
- PMID 26589572.
Delirium is only associated with the antagonism of post‐synaptic M1 receptors and to date other receptor subtypes have not been implicated
- PMID 2849950.
- ^ Edwards Pharmaceuticals, Inc., Belcher Pharmaceuticals, Inc. (May 2010). "DailyMed". U.S. National Library of Medicine. Retrieved 13 January 2013.
- PMID 3220113.
Further reading
- Goyal RK (October 1989). "Muscarinic receptor subtypes. Physiology and clinical implications". The New England Journal of Medicine. 321 (15): 1022–1029. PMID 2674717.
- Brann MR, Ellis J, Jørgensen H, Hill-Eubanks D, Jones SV (1993). "Chapter 12: Muscarinic acetylcholine receptor subtypes: Localization and structure/Function". Cholinergic Function and Dysfunction. Progress in Brain Research. Vol. 98. pp. 121–7. 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): 304–307. 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): 1111–1115. 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): 4703–4707. 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. 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): 146–150. S2CID 4312544.
- Bonner TI, Buckley NJ, Young AC, Brann MR (July 1987). "Identification of a family of muscarinic acetylcholine receptor genes". Science. 237 (4814): 527–532. 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): 3923–3929. 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. 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): 455–462. 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): 21103–21109. 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): 2343–2351. PMID 8139539.
- Offermanns S, Wieland T, Homann D, Sandmann J, Bombien E, Spicher K, et al. (May 1994). "Transfected muscarinic acetylcholine receptors selectively couple to Gi-type G proteins and Gq/11". Molecular Pharmacology. 45 (5): 890–898. 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): 241–245. S2CID 84364768.
- Courseaux A, Grosgeorge J, Gaudray P, Pannett AA, Forbes SA, Williamson C, et al. (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): 354–365. 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): 648–654. 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): 344–347. S2CID 22664866.
External links
- "Acetylcholine receptors (muscarinic): M1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2 January 2015. Retrieved 25 November 2008.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.