The muscarinic acetylcholine receptor M1, also known as the cholinergic receptor, muscarinic 1, is a muscarinic receptor that in humans is encoded by the CHRM1gene.[1] It is localized to 11q13.[1]
This receptor is found mediating slow EPSP at the ganglion in the postganglionic nerve,[2] is common in exocrine glands and in the CNS.[3][4]
It is predominantly found bound to G proteins of class Gq[5][6] 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.
A structural homolog of M1 receptor is expressed in unicellular eukaryotes, such as Acanthamoeba castellanii.[10] and Naegleria fowleri.[11] 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.[8][12] It is preassembled to the Gq heterotrimer through a polybasic c-terminal domain.[5]
↑Messer WS (2000-01-20). "Acetylcholine". University of Toledo. Archived from the original on 14 October 2007. Retrieved 2007-10-27.
↑Johnson G (2002). PDQ Pharmacology (2nd ed.). Hamilton, Ontario: BC Decker Inc. pp. 311 pages. ISBN1-55009-109-3.
↑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. ISBN978-0781701662. Retrieved 2007-10-27.
↑Baig AM, Ahmad HR (2016). "Evidence of a M1-muscarinic GPCR homolog in unicellular eukaryotes: featuring Acanthamoeba spp bioinformatics 3D-modelling and experimentations". Journal of Receptor and Signal Transduction Research: 1–9. doi:10.1080/10799893.2016.1217884. PMID27601178.
↑Baig AM (2016). "Primary Amoebic Meningoencephalitis: Neurochemotaxis and Neurotropic Preferences of Naegleria fowleri". ACS Chemical Neuroscience. 7 (8): 1026–9. doi:10.1021/acschemneuro.6b00197. PMID27447543.
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. PMID1411529.
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. PMID1445347.
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. PMID2739737.
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. PMID3037705.
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. PMID7925360.
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. PMID8063729.
Offermanns S, Wieland T, Homann D, Sandmann J, Bombien E, Spicher K, Schultz G, Jakobs KH (1994). "Transfected muscarinic acetylcholine receptors selectively couple to Gi-type G proteins and Gq/11". Mol. Pharmacol. 45 (5): 890–8. PMID8190105.
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. PMID8508928.
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 (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. PMID8938448.
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. PMID9303164.
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. PMID9518684.