Family
Muscarinic acetylcholine receptor M5 (IPR000502)
Short name:
Musac_Ach_M5_rcpt
Overlapping homologous superfamilies
None.
Family relationships
Description
Muscarinic acetylcholine receptors are members of rhodopsin-like G-protein coupled receptor family. They play several important roles; they mediate many of the effects of acetylcholine in the central and peripheral nervous system and modulate a variety of physiological functions, such as airway, eye and intestinal smooth muscle contraction, heart rate and glandular secretions. The receptors have a widespread tissue distribution and are a major drug target in human disease. They may be effective therapeutic targets in Alzheimer's disease, schizophrenia, Parkinson's disease and chronic obstructive pulmonary disease [PMID: 15850824, PMID: 17762886].
There are five muscarinic acetylcholine receptor subtypes, designated M1-5 [PMID: 3443095, PMID: 3272174, PMID: 3037705, PMID: 9647869, PMID: 2470172]. The family can be further divided into two broad groups based on their primary coupling to G-proteins. M2 and M4 receptors couple to the pertussis-toxin sensitive Gi proteins, whereas M1, M3 and M5 receptors couple to Gq proteins [PMID: 9647869, PMID: 8853955], which activate phospholipase C. The different subtypes can also couple to a wide range of diverse signalling pathways, some of which are G protein-independent [PMID: 10841527, PMID: 14641022, PMID: 12725869].
All subtypes seem to serve as autoreceptors [PMID: 11714883], and knockout mice reveal the important neuromodulatory role played by this receptor family [PMID: 14744253, PMID: 15474550, PMID: 17762886].
The muscarinic acetylcholine M5 receptor is primarily found in the CNS [PMID: 2402490, PMID: 8429821, PMID: 8164520], but is also found in esophageal smooth muscle [PMID: 11082420] and in the heart [PMID: 11306684]. Binding of acetylcholine to the receptor triggers a number of cellular responses, such as adenylate cyclase inhibition [PMID: 14607263], phosphoinositide degradation [PMID: 3272174], and potassium channel modulation [PMID: 7680091]. The receptor has been shown to stimulate gastric acid secretion [PMID: 15691866].
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Douglas CL, Baghdoyan HA, Lydic R.
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Weiner DM, Levey AI, Brann MR.
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Proc. Natl. Acad. Sci. U.S.A. 87 7050-4 1990
Yasuda RP, Ciesla W, Flores LR, Wall SJ, Li M, Satkus SA, Weisstein JS, Spagnola BV, Wolfe BB.
Development of antisera selective for m4 and m5 muscarinic cholinergic receptors: distribution of m4 and m5 receptors in rat brain.
Mol. Pharmacol. 43 149-57 1993
Vilaro MT, Palacios JM, Mengod G.
Multiplicity of muscarinic autoreceptor subtypes? Comparison of the distribution of cholinergic cells and cells containing mRNA for five subtypes of muscarinic receptors in the rat brain.
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Preiksaitis HG, Krysiak PS, Chrones T, Rajgopal V, Laurier LG.
Pharmacological and molecular characterization of muscarinic receptor subtypes in human esophageal smooth muscle.
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Wang H, Han H, Zhang L, Shi H, Schram G, Nattel S, Wang Z.
Expression of multiple subtypes of muscarinic receptors and cellular distribution in the human heart.
Mol. Pharmacol. 59 1029-36 2001
Yamada M, Basile AS, Fedorova I, Zhang W, Duttaroy A, Cui Y, Lamping KG, Faraci FM, Deng CX, Wess J.
Novel insights into M5 muscarinic acetylcholine receptor function by the use of gene targeting technology.
Life Sci. 74 345-53 2003
Bonner TI, Young AC, Brann MR, Buckley NJ.
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Neuron 1 403-10 1988
Jones SV.
Muscarinic receptor subtypes: modulation of ion channels.
Life Sci. 52 457-64 1993
Aihara T, Nakamura Y, Taketo MM, Matsui M, Okabe S.
Cholinergically stimulated gastric acid secretion is mediated by M(3) and M(5) but not M(1) muscarinic acetylcholine receptors in mice.
Am. J. Physiol. Gastrointest. Liver Physiol. 288 G1199-207 2005
GO terms
Biological Process
GO:0007186 G-protein coupled receptor signaling pathway
GO:0001696 gastric acid secretion
Molecular Function
GO:0016907 G-protein coupled acetylcholine receptor activity
Cellular Component
GO:0005887 integral component of plasma membrane
InterPro