WordNet

a measure of the money supply; M2 plus deposits at institutions that are not banks (such as savings and loan associations)
a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response
the 13th letter of the Roman alphabet (同)m
the imperial dynasty of China from 1368 to 1644 (同)Ming dynasty

PrepTutorEJDIC

=sense organ / 受信装置
Mach number / mark[s] / Monsieur
(中国の)明,明朝(1368‐1644)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/08/07 08:56:01」(JST)

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The muscarinic acetylcholine receptor M₃, also known as the cholinergic receptor, muscarinic 3, is a muscarinic acetylcholine receptor. It is encoded by the human gene CHRM3.^[2]

The M₃ muscarinic receptors are located at many places in the body, e.g., smooth muscles, the endocrine glands, the exocrine glands, lungs, pancreas and the brain. In the CNS, they induce emesis. Muscarinic M₃ receptors are expressed in regions of the brain that regulate insulin homeostasis, such as the hypothalamus and dorsal vagal complex of the brainstem.^[3] These receptors are highly expressed on pancreatic beta cells and are critical regulators of glucose homoestasis by modulating insulin secretion.^[4] In general, they cause smooth muscle contraction and increased glandular secretions.^[2]

They are unresponsive to PTX and CTX.

Mechanism

Like the M₁ muscarinic receptor, M₃ receptors are coupled to G proteins of class G_q, which upregulate phospholipase C and, therefore, inositol trisphosphate and intracellular calcium as a signalling pathway.^[5] The calcium function in vertebrates also involves activation of protein kinase C and its effects.

Effects

Smooth muscle

Because the M₃ receptor is G_q-coupled and mediates an increase in intracellular calcium, it typically causes constriction of smooth muscle, such as that observed during bronchoconstriction. However, with respect to vasculature, activation of M₃ on vascular endothelial cells causes increased synthesis of nitric oxide, which diffuses to adjacent vascular smooth muscle cells and causes their relaxation and vasodilation, thereby explaining the paradoxical effect of parasympathomimetics on vascular tone and bronchiolar tone. Indeed, direct stimulation of vascular smooth muscle M₃ mediates vasoconstriction in pathologies wherein the vascular endothelium is disrupted.^[6]

Diabetes

The muscarinic M₃ receptor regulates insulin secretion from the pancreas^[4] and are an important target for understanding the mechanisms of type 2 diabetes mellitus.

Some antipsychotic drugs that are prescribed to treat schizophrenia and bipolar disorder (such as olanzapine and clozapine) have a high risk of diabetes side-effects. These drugs potently bind to and block the muscarinic M₃ receptor, which causes insulin dysregulation that may precede diabetes.^[3]

Other

The M₃ receptors are also located in many glands, both endocrine and exocrine glands, and help to stimulate secretion in salivary glands and other glands of the body.

Other effects are:

increased secretions from stomach
Eye accommodation

Agonists

No highly selective M3 agonists are yet available as of 2009, but a number of non-selective muscarinic agonists are active at M3.

acetylcholine
bethanechol
carbachol^[7]
L-689,660 (mixed M1/M3 agonist)
oxotremorine^[7]
pilocarpine (in eye)

Antagonists

atropine^[5]^[7]
Hyoscyamine^[8]
4-DAMP (1,1-Dimethyl-4-diphenylacetoxypiperidinium iodide, CAS# 1952-15-4)
DAU-5884 (8-Methyl-8-azabicyclo-3-endo[1.2.3]oct-3-yl-1,4-dihydro-2-oxo-3(2H)-quinazolinecarboxylic acid ester, CAS# 131780-47-7)
dicycloverine^[7]
J-104,129 ((aR)-a-Cyclopentyl-a-hydroxy-N-[1-(4-methyl-3-pentenyl)-4-piperidinyl]benzeneacetamide, CAS# 244277-89-2)
HL-031,120 ((3R,2'R)-enantiomer of EA-3167)
tolterodine^[7]
oxybutynin^[7]
ipratropium^[7]
darifenacin
tiotropium
Zamifenacin ((3R)-1-[2-(1-,3-Benzodioxol-5-yl)ethyl]-3-(diphenylmethoxy)piperidine, CAS# 127308-98-9)

Interactions

Muscarinic acetylcholine receptor M3 has been shown to pre-couple with Gq proteins. The polybasic c-tail of the receptor is necessary for the pre-coupling.^[5] It has also been shown interact with Arf6^[9] and ARF1.^[9]

References

^ Kruse, A. C.; Hu, J.; Pan, A. C.; Arlow, D. H.; Rosenbaum, D. M.; Rosemond, E.; Green, H. F.; Liu, T.; Chae, P. S.; Dror, R. O.; Shaw, D. E.; Weis, W. I.; Wess, J. R.; Kobilka, B. K. (2012). "Structure and dynamics of the M3 muscarinic acetylcholine receptor". Nature 482 (7386): 552–556. doi:10.1038/nature10867. PMC 3529910. PMID 22358844. edit
^ ^a ^b "Entrez Gene: CHRM3 cholinergic receptor, muscarinic 3".
^ ^a ^b Weston-Green, K; Huang XF; Lian J; Deng C (May 2012). "Effects of olanzapine on muscarinic M3 receptor binding density in the brain relates to weight gain, plasma insulin and metabolic hormone levels". European Neuropsychopharmacology 22 (5): 364–73. doi:10.1016/j.euroneuro.2011.09.003. PMID 21982116.
^ ^a ^b Gautam, D; et al., (June 2006). "A critical role for [beta] cell M3 muscarinic acetylcholine receptors in regulating insulin release and blood glucose homeostasis in vivo". Cell Metabolism 3 (6): 449–461. doi:10.1016/j.cmet.2006.04.009. PMID 16753580. Cite uses deprecated parameters (help)
^ ^a ^b ^c 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.
^ Keith Parker; Laurence Brunton; Goodman, Louis Sanford; Lazo, John S.; Gilman, Alfred (2006). Goodman & Gilman's the pharmacological basis of therapeutics (11th ed.). New York: McGraw-Hill. pp. page 185. ISBN 0-07-142280-3.
^ ^a ^b ^c ^d ^e ^f ^g Rang HP, Dale MM, Ritter JM, Moore PK (2003). "Ch. 10". Pharmacology (5th ed.). Elsevier Churchill Livingstone. pp. page 139. ISBN 0-443-07145-4.
^ Edwards Pharmaceuticals, Inc.; Belcher Pharmaceuticals, Inc. (May 2010), DailyMed, U.S. National Library of Medicine, retrieved January 13, 2013
^ ^a ^b Mitchell, Rory; Robertson Derek N; Holland Pamela J; Collins Daniel; Lutz Eve M; Johnson Melanie S (September 2003). "ADP-ribosylation factor-dependent phospholipase D activation by the M3 muscarinic receptor". J. Biol. Chem. (United States) 278 (36): 33818–30. doi:10.1074/jbc.M305825200. ISSN 0021-9258. PMID 12799371.

External links

"Acetylcholine receptors (muscarinic): M₃". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.

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English Journal

The muscarinic M3 acetylcholine receptor exists as two differently sized complexes at the plasma membrane.

Patowary S, Alvarez-Curto E, Xu TR, Holz JD, Oliver JA, Milligan G, Raicu V.Source*Physics Department, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, U.S.A.
The Biochemical journal.Biochem J.2013 Jun 1;452(2):303-12. doi: 10.1042/BJ20121902.
The literature on GPCR (G-protein-coupled receptor) homo-oligomerization encompasses conflicting views that range from interpretations that GPCRs must be monomeric, through comparatively newer proposals that they exist as dimers or higher-order oligomers, to suggestions that such quaternary structur
PMID 23521066

State-Dependent Etomidate Occupancy of Its Allosteric Agonist Sites Measured in a Cysteine-Substituted GABAA Receptor.

Stewart DS, Hotta M, Desai R, Forman SA.SourceDepartment of Anesthesia Critical Care & Pain Medicine, Jackson 444, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114. saforman@partners.org.
Molecular pharmacology.Mol Pharmacol.2013 Jun;83(6):1200-8. doi: 10.1124/mol.112.084558. Epub 2013 Mar 22.
A central axiom of ligand-receptor theory is that agonists bind more tightly to active than to inactive receptors. However, measuring agonist affinity in inactive receptors is confounded by concomitant activation. We identified a cysteine substituted mutant γ-aminobutyric acid type A (GABAA) recept
PMID 23525330

Japanese Journal

昆虫RDL GABA受容体の構造と薬剤感受性に関する研究

Journal of Pesticide Science 40(3), 152-159, 2015
NAID 130005094225

昆虫RDL GABA受容体の構造と薬剤感受性に関する研究

Journal of Pesticide Science advpub(0), 2015
NAID 130005087539

2P186 ウシ毛様体筋細胞においてカフェインはムスカリン受容体作動性陽イオンチャネルの活性化を誘起する(12. 細胞生物的課題,ポスター,第52回日本生物物理学会年会(2014年度))

生物物理 54(SUPPLEMENT_1-2), S225, 2014-08-20
NAID 110009932732

「M3受容体」

Cholinergic receptor, muscarinic 3
	; Rat M3 muscarinic acetylcholine receptor/lysozyme fusion protein with bound tiotropium. PDB 4daj
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	2CSA
Identifiers
Symbols	CHRM3 ; EGBRS; HM3
External IDs	OMIM: 118494 MGI: 88398 HomoloGene: 20191 IUPHAR: M3 ChEMBL: 245 GeneCards: CHRM3 Gene
Gene ontology
Molecular function	• phosphatidylinositol phospholipase C activity; • receptor activity; • drug binding; • G-protein coupled acetylcholine receptor activity; • acetylcholine binding;
Cellular component	• plasma membrane; • integral to plasma membrane; • basolateral plasma membrane; • cell junction; • dendrite; • asymmetric synapse; • axon terminus; • postsynaptic membrane;
Biological process	• regulation of vascular smooth muscle contraction; • energy reserve metabolic process; • cellular protein modification process; • smooth muscle contraction; • signal transduction; • G-protein coupled receptor signaling pathway; • nervous system development; • digestion; • cell proliferation; • regulation of ion transport; • small molecule metabolic process; • positive regulation of smooth muscle contraction; • regulation of insulin secretion; • regulation of phospholipase C activity;
	Sources: Amigo / QuickGO
Orthologs
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