Muscarinic acetylcholine receptor M3: Difference between revisions

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Latest revision as of 19:51, 6 November 2018

The muscarinic acetylcholine receptor, also known as cholinergic/acetylcholine receptor M₃, or the muscarinic 3, is a muscarinic acetylcholine receptor encoded by the human gene CHRM3.^[1]

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.^[2] These receptors are highly expressed on pancreatic beta cells and are critical regulators of glucose homoestasis by modulating insulin secretion.^[3] In general, they cause smooth muscle contraction and increased glandular secretions.^[1]

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.^[4] 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.^[5]

Diabetes

The muscarinic M₃ receptor regulates insulin secretion from the pancreas^[3] 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.^[2]

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 2018, but a number of non-selective muscarinic agonists are active at M3.

acetylcholine
bethanechol
carbachol^[6]
L-689,660 (mixed M1/M3 agonist)
oxotremorine^[6]
pilocarpine (in eye)

Antagonists

atropine^[4]^[6]
hyoscyamine^[7]

aclidinium bromide
4-DAMP (1,1-Dimethyl-4-diphenylacetoxypiperidinium iodide, CAS# 1952-15-4)
darifenacin
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^[6]
HL-031,120 ((3R,2'R)-enantiomer of EA-3167)
ipratropium^[6]
J-104,129 ((aR)-a-Cyclopentyl-a-hydroxy-N-[1-(4-methyl-3-pentenyl)-4-piperidinyl]benzeneacetamide, CAS# 244277-89-2)
oxybutynin^[6]
tiotropium
tolterodine^[6]
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.^[4] It has also been shown interact with Arf6^[8] and ARF1.^[8]

References

↑ ^1.0 ^1.1 "Entrez Gene: CHRM3 cholinergic receptor, muscarinic 3".
↑ ^2.0 ^2.1 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.
↑ ^3.0 ^3.1 Gautam D, Han SJ, Hamdan FF, Jeon J, Li B, Li JH, Cui Y, Mears D, Lu H, Deng C, Heard T, Wess J (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.
↑ ^4.0 ^4.1 ^4.2 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.
↑ 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. p. 185. ISBN 0-07-142280-3.
↑ ^6.0 ^6.1 ^6.2 ^6.3 ^6.4 ^6.5 ^6.6 Rang HP, Dale MM, Ritter JM, Moore PK (2003). "Ch. 10". Pharmacology (5th ed.). Elsevier Churchill Livingstone. p. 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
↑ ^8.0 ^8.1 Mitchell R, Robertson DN, Holland PJ, Collins D, Lutz EM, Johnson MS (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.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

[entrezM3-1] 1.0 ^1.1 "Entrez Gene: CHRM3 cholinergic receptor, muscarinic 3".

[Weston-Green_2012_364–73-2] 2.0 ^2.1 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.

[Gautam_2006_449–461-3] 3.0 ^3.1 Gautam D, Han SJ, Hamdan FF, Jeon J, Li B, Li JH, Cui Y, Mears D, Lu H, Deng C, Heard T, Wess J (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.

[Kou_Qin-4] 4.0 ^4.1 ^4.2 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.

[isbn0-07-142280-3-5] 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. p. 185. ISBN 0-07-142280-3.

[Rang-6] 6.0 ^6.1 ^6.2 ^6.3 ^6.4 ^6.5 ^6.6 Rang HP, Dale MM, Ritter JM, Moore PK (2003). "Ch. 10". Pharmacology (5th ed.). Elsevier Churchill Livingstone. p. 139. ISBN 0-443-07145-4.

[7] Edwards Pharmaceuticals, Inc.; Belcher Pharmaceuticals, Inc. (May 2010), DailyMed, U.S. National Library of Medicine, retrieved January 13, 2013

[pmid12799371-8] 8.0 ^8.1 Mitchell R, Robertson DN, Holland PJ, Collins D, Lutz EM, Johnson MS (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.

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@@ Line 1: / Line 1: @@
-{{Wrongtitle|title=Muscarinic acetylcholine receptor M<sub>3</sub>}}
+{{DISPLAYTITLE:Muscarinic acetylcholine receptor M<sub>3</sub>}}
-<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
+{{Infobox_gene}}
-{{PBB_Controls
-| update_page = yes
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-<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
+The '''muscarinic acetylcholine receptor''', also known as '''cholinergic/acetylcholine receptor M<sub>3</sub>''', or the '''muscarinic 3''', is a [[muscarinic acetylcholine receptor]] encoded by the human gene '''CHRM3'''.<ref name="entrezM3"/>
-{{GNF_Protein_box
- | image =
- | image_source =
- | PDB =
- | Name = Cholinergic receptor, muscarinic 3
- | HGNCid = 1952
- | Symbol = CHRM3
- | AltSymbols =; HM3
- | OMIM = 118494
- | ECnumber =
- | Homologene = 20191
- | MGIid = 88398
- | Function = {{GNF_GO|id=GO:0001584 |text = rhodopsin-like receptor activity}} {{GNF_GO|id=GO:0004435 |text = phosphoinositide phospholipase C activity}} {{GNF_GO|id=GO:0004872 |text = receptor activity}} {{GNF_GO|id=GO:0004981 |text = muscarinic acetylcholine receptor activity}}
- | Component = {{GNF_GO|id=GO:0005886 |text = plasma membrane}} {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}} {{GNF_GO|id=GO:0016021 |text = integral to membrane}} {{GNF_GO|id=GO:0045211 |text = postsynaptic membrane}}
- | Process = {{GNF_GO|id=GO:0006464 |text = protein modification process}} {{GNF_GO|id=GO:0006939 |text = smooth muscle contraction}} {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007186 |text = G-protein coupled receptor protein signaling pathway}} {{GNF_GO|id=GO:0007399 |text = nervous system development}} {{GNF_GO|id=GO:0007586 |text = digestion}} {{GNF_GO|id=GO:0008283 |text = cell proliferation}} {{GNF_GO|id=GO:0045987 |text = positive regulation of smooth muscle contraction}}
- | Orthologs = {{GNF_Ortholog_box
-    | Hs_EntrezGene = 1131
-    | Hs_Ensembl =
-    | Hs_RefseqProtein = XP_001130695
-    | Hs_RefseqmRNA = XM_001130695
-    | Hs_GenLoc_db =
-    | Hs_GenLoc_chr =
-    | Hs_GenLoc_start =
-    | Hs_GenLoc_end =
-    | Hs_Uniprot =
-    | Mm_EntrezGene = 12671
-    | Mm_Ensembl = ENSMUSG00000046159
-    | Mm_RefseqmRNA = NM_033269
-    | Mm_RefseqProtein = NP_150372
-    | Mm_GenLoc_db =
-    | Mm_GenLoc_chr = 13
-    | Mm_GenLoc_start = 9876475
-    | Mm_GenLoc_end = 9878244
-    | Mm_Uniprot = Q542R4
-  }}
-}}
-The '''muscarinic acetylcholine receptor M<sub>3</sub>''', also known as the '''cholinergic receptor, muscarinic 3''', is a [[muscarinic acetylcholine receptor]]. It is encoded by the human gene '''CHRM3'''.<ref name="entrezM3"/>
-The M<sub>3</sub> muscarinic receptors are located at many places in the body, e.g. smooth muscles, [[endocrine gland|endocrine]], in [[exocrine glands]], as well as in the lungs. They are also found in the [[central nervous system|CNS]], where it induces [[emesis]] They generally cause smooth muscle contraction and increased glandular secretions.<ref name="entrezM3">{{cite web | title = Entrez Gene: CHRM3 cholinergic receptor, muscarinic 3| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1131| accessdate = }}</ref>
+The M<sub>3</sub> muscarinic receptors are located at many places in the body, e.g., smooth muscles, the [[endocrine gland|endocrine]] glands, the [[exocrine glands]], lungs, pancreas and the brain. In the [[central nervous system|CNS]], they induce [[emesis]]. Muscarinic M<sub>3</sub> receptors are expressed in regions of the brain that regulate insulin homeostasis, such as the hypothalamus and dorsal vagal complex of the brainstem.<ref name="Weston-Green 2012 364–73">{{cite journal | vauthors = Weston-Green K, Huang XF, Lian J, Deng C | title = Effects of olanzapine on muscarinic M3 receptor binding density in the brain relates to weight gain, plasma insulin and metabolic hormone levels | journal = European Neuropsychopharmacology | volume = 22 | issue = 5 | pages = 364–73 | date = May 2012 | pmid = 21982116 | doi = 10.1016/j.euroneuro.2011.09.003 | url = http://ro.uow.edu.au/hbspapers/2907/ }}</ref> These receptors are highly expressed on pancreatic beta cells and are critical regulators of glucose homoestasis by modulating insulin secretion.<ref name="Gautam 2006 449–461">{{cite journal | vauthors = Gautam D, Han SJ, Hamdan FF, Jeon J, Li B, Li JH, Cui Y, Mears D, Lu H, Deng C, Heard T, Wess J | title = A critical role for [beta] cell M3 muscarinic acetylcholine receptors in regulating insulin release and blood glucose homeostasis in vivo | journal = Cell Metabolism | volume = 3 | issue = 6 | pages = 449–461 | date = June 2006 | pmid = 16753580 | doi = 10.1016/j.cmet.2006.04.009 }}</ref> In general, they cause smooth muscle contraction and increased glandular secretions.<ref name="entrezM3">{{cite web | title = Entrez Gene: CHRM3 cholinergic receptor, muscarinic 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1131| accessdate = }}</ref>
 They are unresponsive to [[pertussis toxin|PTX]] and [[Cholera toxin|CTX]].
 ==Mechanism==
-Like the M<sub>1</sub> muscarinic receptor, M<sub>3</sub> receptors are G proteins of class [[Gq alpha subunit|G<sub>q</sub>]] which upregulate [[phospholipase C]] and therefore [[inositol trisphosphate]] and intracellular [[calcium]] as a signalling pathway. The [[calcium function in humans]] also involves activation of [[protein kinase C]] and its effects.
+Like the M<sub>1</sub> muscarinic receptor, M<sub>3</sub> receptors are coupled to G proteins of class [[Gq alpha subunit|G<sub>q</sub>]], which upregulate [[phospholipase C]] and, therefore, [[inositol trisphosphate]] and intracellular [[calcium]] as a signalling pathway.<ref name="Kou Qin">{{cite journal | vauthors = Qin K, Dong C, Wu G, Lambert NA | title = Inactive-state preassembly of Gq-coupled receptors and Gq heterotrimers | journal = Nature Chemical Biology | volume = 7 | issue = 11 | pages = 740–747 | date = August 2011 | pmid = 21873996 | pmc = 3177959 | doi = 10.1038/nchembio.642 }}</ref> The [[calcium function in vertebrates]] also involves activation of [[protein kinase C]] and its effects.
 ==Effects==
 ===Smooth muscle===
-Because the M<sub>3</sub> receptor is [[Gq alpha subunit|G<sub>q</sub>]]-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 M<sub>3</sub> 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 M<sub>3</sub> mediates [[vasoconstriction]] in pathologies whereby the vascular endothelium is disrupted.<ref name="isbn0-07-142280-3">{{cite book | author = Keith Parker; Laurence Brunton; Goodman, Louis Sanford; Lazo, John S.; Gilman, Alfred | title = Goodman & Gilman's the pharmacological basis of therapeutics | publisher = McGraw-Hill | location = New York | edition = 11<sup>th</sup> Ed. | year = 2006 | pages = page 185 | isbn = 0-07-142280-3 | oclc = | doi = }}</ref>
+Because the M<sub>3</sub> receptor is [[Gq alpha subunit|G<sub>q</sub>]]-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 M<sub>3</sub> 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 M<sub>3</sub> mediates [[vasoconstriction]] in pathologies wherein the vascular endothelium is disrupted.<ref name="isbn0-07-142280-3">{{cite book |author1=Keith Parker |author2=Laurence Brunton |author3=Goodman, Louis Sanford |author4=Lazo, John S. |author5=Gilman, Alfred | title = Goodman & Gilman's the pharmacological basis of therapeutics | publisher = McGraw-Hill | location = New York | edition = 11th | year = 2006 | pages = 185 | isbn = 0-07-142280-3 | oclc = | doi = }}</ref>
+===Diabetes===
+The muscarinic M<sub>3</sub> receptor regulates insulin secretion from the pancreas<ref name="Gautam 2006 449–461"/> 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 M<sub>3</sub> receptor, which causes insulin dysregulation that may precede diabetes.<ref name="Weston-Green 2012 364–73"/>
 ===Other===
@@ Line 63: / Line 25: @@
 Other effects are:
 *increased  secretions from [[stomach]]
 *[[Accommodation (eye)|Eye accommodation]]
 ==Agonists==
+No highly selective M3 agonists are yet available as of 2018, but a number of non-selective muscarinic agonists are active at M3.
 *[[acetylcholine]]
 *[[bethanechol]]
-*[[carbachol]]<ref name=Rang>{{cite book | first = | last =Rang HP, Dale MM, Ritter JM, Moore PK| authorlink = | coauthors = | year = 2003| month = | title =  Pharmacology | chapter = Ch. 10 | editor = | others = | edition = 5<sup>th</sup> edition | pages = page 139 | publisher = Elsevier Churchill Livingstone| location = | id = ISBN 0-443-07145-4| url = }}</ref>
+*[[carbachol]]<ref name="Rang">{{cite book |vauthors=Rang HP, Dale MM, Ritter JM, Moore PK | year = 2003| title =  Pharmacology | chapter = Ch. 10 | edition = 5th | pages = 139 | publisher = Elsevier Churchill Livingstone| location = | isbn = 0-443-07145-4| url = }}</ref>
-*[[oxotremorine]]<ref name=Rang/>
+* L-689,660 (mixed M1/M3 agonist)
+*[[oxotremorine]]<ref name="Rang"/>
 *[[pilocarpine]] (in eye)
 ==Antagonists==
-*[[atropine]]<ref name=Rang/>
+* [[atropine]]<ref name="Kou Qin"/><ref name="Rang"/>
-*[[dicycloverine]]<ref name=Rang/>
+* [[hyoscyamine]]<ref>{{Citation
-*[[tolterodine]]<ref name=Rang/>
+ | last = Edwards Pharmaceuticals, Inc. | first =
-*[[oxybutynin]]<ref name=Rang/>
+ | author-link =
-*[[ipratropium]]<ref name=Rang/>
+ | last2 = Belcher Pharmaceuticals, Inc.
-*[[darifenacin]]
+ | first2 =
-*[[tiotropium]]
+ | author2-link =
+ | title = DailyMed
+ | publisher = U.S. National Library of Medicine
+ | date = May 2010
+ | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=f33a4774-9fbb-4782-a7e1-068e83b7504d
+ | accessdate = January 13, 2013}}
+</ref>
-==See also==
+* [[aclidinium bromide]]
+* 4-DAMP (1,1-Dimethyl-4-diphenylacetoxypiperidinium iodide, CAS# 1952-15-4)
+* [[darifenacin]]
+* 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]]<ref name="Rang"/>
+* HL-031,120 ((3R,2'R)-enantiomer of [[EA-3167]])
+* [[ipratropium]]<ref name="Rang"/>
+* J-104,129 ((aR)-a-Cyclopentyl-a-hydroxy-N-[1-(4-methyl-3-pentenyl)-4-piperidinyl]benzeneacetamide, CAS# 244277-89-2)
+* [[oxybutynin]]<ref name="Rang"/>
+* [[tiotropium]]
+* [[tolterodine]]<ref name="Rang"/>
+* [[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.<ref name="Kou Qin"/> It has also been shown [[Protein-protein interaction|interact]] with [[Arf6]]<ref name=pmid12799371>{{cite journal | vauthors = Mitchell R, Robertson DN, Holland PJ, Collins D, Lutz EM, Johnson MS | title = ADP-ribosylation factor-dependent phospholipase D activation by the M3 muscarinic receptor | language =  | journal = J. Biol. Chem. | volume = 278 | issue = 36 | pages = 33818–30 | date = September 2003 | pmid = 12799371 | doi = 10.1074/jbc.M305825200 | url =  | laysummary =  | oclc =  | id =  | bibcode =  | accessdate =  | location = United States | laydate =  | format =  | quote =  | publisher =  | issn = 0021-9258 | laysource =  }}</ref> and [[ARF1]].<ref name=pmid12799371/>
+== See also ==
 * [[Muscarinic acetylcholine receptor]]
-==References==
+== References ==
-{{reflist|2}}
+{{reflist|35em}}
-==Further reading==
+== Further reading ==
-{{refbegin | 2}}
+{{refbegin|35em}}
-{{PBB_Further_reading
+* {{cite journal | vauthors = Goyal RK | title = Muscarinic receptor subtypes. Physiology and clinical implications. | journal = N. Engl. J. Med. | volume = 321 | issue = 15 | pages = 1022–9 | year = 1989 | pmid = 2674717 | doi = 10.1056/NEJM198910123211506}}
-| citations =
+* {{cite journal | vauthors = Eglen RM, Reddy H, Watson N, Challiss RA | title = Muscarinic acetylcholine receptor subtypes in smooth muscle. | journal = Trends Pharmacol. Sci. | volume = 15 | issue = 4 | pages = 114–9 | year = 1994 | pmid = 8016895 | doi = 10.1016/0165-6147(94)90047-7 }}
-*{{cite journal  | author=Goyal RK |title=Muscarinic receptor subtypes. Physiology and clinical implications. |journal=N. Engl. J. Med. |volume=321 |issue= 15 |pages= 1022-9 |year= 1989 |pmid= 2674717 |doi=  }}
+* {{cite journal | vauthors = Brann MR, Ellis J, Jørgensen H, Hill-Eubanks D, Jones SV | title = Muscarinic acetylcholine receptor subtypes: localization and structure/function. | journal = Prog. Brain Res. | volume = 98 | issue =  | pages = 121–7 | year = 1994 | pmid = 8248499 | doi = 10.1016/S0079-6123(08)62388-2 }}
-*{{cite journal  | author=Eglen RM, Reddy H, Watson N, Challiss RA |title=Muscarinic acetylcholine receptor subtypes in smooth muscle. |journal=Trends Pharmacol. Sci. |volume=15 |issue= 4 |pages= 114-9 |year= 1994 |pmid= 8016895 |doi=  }}
+* {{cite journal | vauthors = Gutkind JS, Novotny EA, Brann MR, Robbins KC | title = Muscarinic acetylcholine receptor subtypes as agonist-dependent oncogenes. | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 88 | issue = 11 | pages = 4703–7 | year = 1991 | pmid = 1905013 | pmc = 51734 | doi = 10.1073/pnas.88.11.4703 | bibcode = 1991PNAS...88.4703G }}
-*{{cite journal  | author=Brann MR, Ellis J, Jørgensen H, ''et al.'' |title=Muscarinic acetylcholine receptor subtypes: localization and structure/function. |journal=Prog. Brain Res. |volume=98 |issue=  |pages= 121-7 |year= 1994 |pmid= 8248499 |doi=  }}
+* {{cite journal | vauthors = Ashkenazi A, Ramachandran J, Capon DJ | title = Acetylcholine analogue stimulates DNA synthesis in brain-derived cells via specific muscarinic receptor subtypes. | journal = Nature | volume = 340 | issue = 6229 | pages = 146–50 | year = 1989 | pmid = 2739737 | doi = 10.1038/340146a0 | bibcode = 1989Natur.340..146A }}
-*{{cite journal  | author=Gutkind JS, Novotny EA, Brann MR, Robbins KC |title=Muscarinic acetylcholine receptor subtypes as agonist-dependent oncogenes. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=88 |issue= 11 |pages= 4703-7 |year= 1991 |pmid= 1905013 |doi=  }}
+* {{cite journal | vauthors = Bonner TI, Buckley NJ, Young AC, Brann MR | title = Identification of a family of muscarinic acetylcholine receptor genes. | journal = Science | volume = 237 | issue = 4814 | pages = 527–32 | year = 1987 | pmid = 3037705 | doi = 10.1126/science.3037705 | bibcode = 1987Sci...237..527B }}
-*{{cite journal  | author=Ashkenazi A, Ramachandran J, Capon DJ |title=Acetylcholine analogue stimulates DNA synthesis in brain-derived cells via specific muscarinic receptor subtypes. |journal=Nature |volume=340 |issue= 6229 |pages= 146-50 |year= 1989 |pmid= 2739737 |doi= 10.1038/340146a0 }}
+* {{cite journal | vauthors = Bonner TI, Young AC, Brann MR, Buckley NJ | title = Cloning and expression of the human and rat m5 muscarinic acetylcholine receptor genes. | journal = Neuron | volume = 1 | issue = 5 | pages = 403–10 | year = 1990 | pmid = 3272174 | doi = 10.1016/0896-6273(88)90190-0 }}
-*{{cite journal  | author=Bonner TI, Buckley NJ, Young AC, Brann MR |title=Identification of a family of muscarinic acetylcholine receptor genes. |journal=Science |volume=237 |issue= 4814 |pages= 527-32 |year= 1987 |pmid= 3037705 |doi=  }}
+* {{cite journal | vauthors = Peralta EG, Ashkenazi A, Winslow JW, Smith DH, Ramachandran J, Capon DJ | title = Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors. | journal = EMBO J. | volume = 6 | issue = 13 | pages = 3923–9 | year = 1988 | pmid = 3443095 | pmc = 553870 | doi =  }}
-*{{cite journal  | author=Bonner TI, Young AC, Brann MR, Buckley NJ |title=Cloning and expression of the human and rat m5 muscarinic acetylcholine receptor genes. |journal=Neuron |volume=1 |issue= 5 |pages= 403-10 |year= 1990 |pmid= 3272174 |doi=  }}
+* {{cite journal | vauthors = Blin N, Yun J, Wess J | title = Mapping of single amino acid residues required for selective activation of Gq/11 by the m3 muscarinic acetylcholine receptor. | journal = J. Biol. Chem. | volume = 270 | issue = 30 | pages = 17741–8 | year = 1995 | pmid = 7629074 | doi = 10.1074/jbc.270.30.17741 }}
-*{{cite journal  | author=Peralta EG, Ashkenazi A, Winslow JW, ''et al.'' |title=Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors. |journal=EMBO J. |volume=6 |issue= 13 |pages= 3923-9 |year= 1988 |pmid= 3443095 |doi=  }}
+* {{cite journal | vauthors = Crespo P, Xu N, Daniotti JL, Troppmair J, Rapp UR, Gutkind JS | title = Signaling through transforming G protein-coupled receptors in NIH 3T3 cells involves c-Raf activation. Evidence for a protein kinase C-independent pathway. | journal = J. Biol. Chem. | volume = 269 | issue = 33 | pages = 21103–9 | year = 1994 | pmid = 8063729 | doi =  }}
-*{{cite journal  | author=Blin N, Yun J, Wess J |title=Mapping of single amino acid residues required for selective activation of Gq/11 by the m3 muscarinic acetylcholine receptor. |journal=J. Biol. Chem. |volume=270 |issue= 30 |pages= 17741-8 |year= 1995 |pmid= 7629074 |doi=  }}
+* {{cite journal | vauthors = Haga K, Kameyama K, Haga T, Kikkawa U, Shiozaki K, Uchiyama H | title = Phosphorylation of human m1 muscarinic acetylcholine receptors by G protein-coupled receptor kinase 2 and protein kinase C. | journal = J. Biol. Chem. | volume = 271 | issue = 5 | pages = 2776–82 | year = 1996 | pmid = 8576254 | doi = 10.1074/jbc.271.5.2776 }}
-*{{cite journal  | author=Crespo P, Xu N, Daniotti JL, ''et al.'' |title=Signaling through transforming G protein-coupled receptors in NIH 3T3 cells involves c-Raf activation. Evidence for a protein kinase C-independent pathway. |journal=J. Biol. Chem. |volume=269 |issue= 33 |pages= 21103-9 |year= 1994 |pmid= 8063729 |doi=  }}
+* {{cite journal | vauthors = Szekeres PG, Koenig JA, Edwardson JM | title = The relationship between agonist intrinsic activity and the rate of endocytosis of muscarinic receptors in a human neuroblastoma cell line. | journal = Mol. Pharmacol. | volume = 53 | issue = 4 | pages = 759–65 | year = 1998 | pmid = 9547368 | doi =  }}
-*{{cite journal  | author=Haga K, Kameyama K, Haga T, ''et al.'' |title=Phosphorylation of human m1 muscarinic acetylcholine receptors by G protein-coupled receptor kinase 2 and protein kinase C. |journal=J. Biol. Chem. |volume=271 |issue= 5 |pages= 2776-82 |year= 1996 |pmid= 8576254 |doi=  }}
+* {{cite journal | vauthors = von der Kammer H, Mayhaus M, Albrecht C, Enderich J, Wegner M, Nitsch RM | title = Muscarinic acetylcholine receptors activate expression of the EGR gene family of transcription factors. | journal = J. Biol. Chem. | volume = 273 | issue = 23 | pages = 14538–44 | year = 1998 | pmid = 9603968 | doi = 10.1074/jbc.273.23.14538 }}
-*{{cite journal  | author=Szekeres PG, Koenig JA, Edwardson JM |title=The relationship between agonist intrinsic activity and the rate of endocytosis of muscarinic receptors in a human neuroblastoma cell line. |journal=Mol. Pharmacol. |volume=53 |issue= 4 |pages= 759-65 |year= 1998 |pmid= 9547368 |doi=  }}
+* {{cite journal | vauthors = Ndoye A, Buchli R, Greenberg B, Nguyen VT, Zia S, Rodriguez JG, Webber RJ, Lawry MA, Grando SA | title = Identification and mapping of keratinocyte muscarinic acetylcholine receptor subtypes in human epidermis. | journal = J. Invest. Dermatol. | volume = 111 | issue = 3 | pages = 410–6 | year = 1998 | pmid = 9740233 | doi = 10.1046/j.1523-1747.1998.00299.x }}
-*{{cite journal  | author=von der Kammer H, Mayhaus M, Albrecht C, ''et al.'' |title=Muscarinic acetylcholine receptors activate expression of the EGR gene family of transcription factors. |journal=J. Biol. Chem. |volume=273 |issue= 23 |pages= 14538-44 |year= 1998 |pmid= 9603968 |doi=  }}
+* {{cite journal | vauthors = Goodchild RE, Court JA, Hobson I, Piggott MA, Perry RH, Ince P, Jaros E, Perry EK | title = Distribution of histamine H3-receptor binding in the normal human basal ganglia: comparison with Huntington's and Parkinson's disease cases. | journal = Eur. J. Neurosci. | volume = 11 | issue = 2 | pages = 449–56 | year = 1999 | pmid = 10051746 | doi = 10.1046/j.1460-9568.1999.00453.x }}
-*{{cite journal  | author=Ndoye A, Buchli R, Greenberg B, ''et al.'' |title=Identification and mapping of keratinocyte muscarinic acetylcholine receptor subtypes in human epidermis. |journal=J. Invest. Dermatol. |volume=111 |issue= 3 |pages= 410-6 |year= 1998 |pmid= 9740233 |doi= 10.1046/j.1523-1747.1998.00299.x }}
+* {{cite journal | vauthors = Sato KZ, Fujii T, Watanabe Y, Yamada S, Ando T, Kazuko F, Kawashima K | title = Diversity of mRNA expression for muscarinic acetylcholine receptor subtypes and neuronal nicotinic acetylcholine receptor subunits in human mononuclear leukocytes and leukemic cell lines. | journal = Neurosci. Lett. | volume = 266 | issue = 1 | pages = 17–20 | year = 1999 | pmid = 10336173 | doi = 10.1016/S0304-3940(99)00259-1 }}
-*{{cite journal  | author=Goodchild RE, Court JA, Hobson I, ''et al.'' |title=Distribution of histamine H3-receptor binding in the normal human basal ganglia: comparison with Huntington's and Parkinson's disease cases. |journal=Eur. J. Neurosci. |volume=11 |issue= 2 |pages= 449-56 |year= 1999 |pmid= 10051746 |doi=  }}
+* {{cite journal | vauthors = Budd DC, McDonald JE, Tobin AB | title = Phosphorylation and regulation of a Gq/11-coupled receptor by casein kinase 1alpha. | journal = J. Biol. Chem. | volume = 275 | issue = 26 | pages = 19667–75 | year = 2000 | pmid = 10777483 | doi = 10.1074/jbc.M000492200 }}
-*{{cite journal  | author=Sato KZ, Fujii T, Watanabe Y, ''et al.'' |title=Diversity of mRNA expression for muscarinic acetylcholine receptor subtypes and neuronal nicotinic acetylcholine receptor subunits in human mononuclear leukocytes and leukemic cell lines. |journal=Neurosci. Lett. |volume=266 |issue= 1 |pages= 17-20 |year= 1999 |pmid= 10336173 |doi=  }}
-*{{cite journal  | author=Budd DC, McDonald JE, Tobin AB |title=Phosphorylation and regulation of a Gq/11-coupled receptor by casein kinase 1alpha. |journal=J. Biol. Chem. |volume=275 |issue= 26 |pages= 19667-75 |year= 2000 |pmid= 10777483 |doi= 10.1074/jbc.M000492200 }}
-}}
 {{refend}}
+== External links ==
+* {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2143 | title = Acetylcholine receptors (muscarinic): M<sub>3</sub>  | accessdate = | format = | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | pages = | archiveurl = | archivedate = | quote = }}
 {{NLM content}}
-{{membrane-protein-stub}}
 {{G protein-coupled receptors}}
-[[Category:G protein coupled receptors]]
+{{Muscarinic acetylcholine receptor modulators}}
+{{DEFAULTSORT:Muscarinic Acetylcholine Receptor M3}}
-[[es:Receptor muscarínico M3]]
+[[Category:Muscarinic acetylcholine receptors]]