Izvorni kod stranice Muskarinski acetilholinski receptor M2

{{DISPLAYTITLE:Muskarinski acetilholinski receptor M<sub>2</sub>}}
{{PBB|geneid=1129}}
'''Muskarinski acetilholinski receptor M<sub>2</sub>''' (''holinergički receptor, muskarinski 2'') je [[muskarinski acetilholinski receptor]].

== Funkcija ==
=== Srce ===
M2 muskarinski receptori su locirani u srcu, gde usporavaju [[brzina srca|brzinu srca]] do normalnog [[sinusni ritam|sinusnog ritma]] nakon stimulatornog dejstva [[Simpatički nervni sistem|simpatetičkog nervnog sistema]], putem usporavanja brzine [[depolarizacija|depolarizacije]]. Oni takođe redukuju kontraktilne sile [[Srčana pretkomora|atrijalnog]] srčanog mišića, i umanjuju provodnu brzinu [[atrioventrikularnog čvora]] (AV čvor). Oni nemaju efekta na kontrakcione sile [[Srčana komora|ventrikularnog]] mišića.

=== IQ ===
Jedna danska porodična studija iz 2006 je utvrdila da postoji "veoma značajna veze" između {{Gene|CHRM2}} [[gen]]a i inteligencije. Ova studija je koristila uzorak od 667 osoba iz 304 porodice.<ref>{{cite journal |author=Gosso MF, van Belzen M, de Geus EJ, ''et al.'' |title=Association between the CHRM2 gene and intelligence in a sample of 304 Dutch families |journal=Genes, Brain and Behavior |volume=5 |issue=8 pages=577–584 |year=2006 |pmid=17081262 |doi=10.1111/j.1601-183X.2006.00211.x |url=}}</ref> Slična veza je nezavisno nađena u studiji blizanaca i porodica u Minesoti.<ref>{{cite journal  |author=Dick DM, Aliev F, Kramer J, ''et al.''  |title=Association of CHRM2 with IQ: converging evidence for a gene influencing intelligence |journal=Behav. Genet. |volume=37 |issue=2 |pages=265–272 |year=2007 |pmid=17160701 |doi=10.1007/s10519-006-9131-2 |url=https://archive.org/details/sim_behavior-genetics_2007-03_37_2/page/265}}</ref> Međutim, kasniji pokušaji iz [[2009.]] da se potvrde ove tvrdnje je bili neuspešni.<ref>{{cite journal |author=Lind PA, Luciano M, Horan MA, ''et al.'' |title=No association between Cholinergic Muscarinic Receptor 2 (CHRM2) genetic variation and cognitive abilities in three independent samples |journal=Behav. Genet. |volume=39 |issue=5 |pages=513–23 |year=2009 |month=September |pmid=19418213 |doi=10.1007/s10519-009-9274-z |url=https://archive.org/details/sim_behavior-genetics_2009-09_39_5/page/513}}</ref>

== Mehanizam ==
M2 muskarinski receptori deluju putem [[Gi alfa podjedinica|G<sub>i</sub>]] tipa receptora, koji uzrokuju smanjenje cAMP koncentracije u ćeliji, generalno dovodeći do inhibitornih efekata.

Oni takođe moduliraju [[kalijumov kanal|muskarinske kalijumove kanale]].<ref name="Rang">{{Cite book |author=Rang, H. P. |title=Pharmacology |url=https://archive.org/details/isbn_9788181479174 |publisher=Churchill Livingstone |location=Edinburgh |year=2003 |pages= |isbn=0-443-07145-4 |oclc= |doi=}}</ref><ref name="Boron">{{Cite book |author=Boron, W. F and Boulpaep, E. L. |title=Medical Physiology |url=https://archive.org/details/medicalphysiolog0000boro |publisher=Elsevier Saunders |location=Philadelphia |year=2005 |pages=[https://archive.org/details/medicalphysiolog0000boro/page/387 387] |isbn=1-4160-2328-3 |oclc= |doi=}}</ref> U srcu, oni doprinose smanjenju brzine rada srca.

== Gen ==
Muskarinski acetilholinski receptor M2 je kodiran genom {{gene|CHRM2}}.<ref name="entrez">{{cite web | title = Entrez Gene: CHRM2 cholinergic receptor, muscarinic 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1129| accessdate = }}</ref> Višestruke [[Alternativno splajsovanje|alternativno splajsovane]] [[Transkripcija (genetika)|transkriptne]] varijante ovog gene au nađene.<ref name="entrez"/>

== Ligandi ==
Nekoliko visoko selektivnih M2 agonista je trenutno dostupno. Brojni neselektivni agonisti i antagonisti su poznati.

=== Agonisti ===
* [[Betanehol]] (neselektivni muskarinski agonist)
* (2S,2'R,3'S,5'R)-1-methil-2-(2-methil-1,3-oksatiolan-5-il)pirolidin 3-sulfokside metil jodid (selektivni [[Parcijalni agonist|parcijalni]] M2 agonist)<ref name="pmid16539379">{{cite journal | author = Scapecchi S, Matucci R, Bellucci C, Buccioni M, Dei S, Guandalini L, Martelli C, Manetti D, Martini E, Marucci G, Nesi M, Romanelli MN, Teodori E, Gualtieri F | title = Highly chiral muscarinic ligands: the discovery of (2S,2'R,3'S,5'R)-1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine 3-sulfoxide methyl iodide, a potent, functionally selective, M2 partial agonist | journal = J. Med. Chem. | volume = 49 | issue = 6 | pages = 1925–31 | year = 2006 | month = March | pmid = 16539379 | doi = 10.1021/jm0510878 | url =  }}</ref>

=== Antagonisti ===
* [[Dimetinden]] - N,N-Dimetil-3-[(1S)-1-(2-piridinil)etil]-1H-inden-2-etanamin, CAS# 121367-05-3, mešoviti M2 / histamin H1 antagonist
* Otenzepad - 11-([2-[(Dietilamino)metil]-1-piperidinil]acetil)-5,11-dihidro-6H-pirido[2,3-b][1,4]benzodiazepin-6-on, CAS# 102394-31-0
* AQRA-741 - 11-([4-[4-(Dietilamino)butil]-1-piperidinil]acetil)-5,11-dihidro-6H-pirido[2,3-b][1,4]benzodiazepin-6-on, CAS# 123548-16-3
* [[AFDX-384]] (mešoviti M2/M4 antagonist) - N-[2-[2-[(Dipropilamino)metil]-1-piperidinil]etil]-5,6-dihidro-6-okso-11H-pirido[2,3-b][1,4]benzodiazepin-11-karboksamid, CAS# 118290-27-0

== Povezano ==
* [[Muskarinski acetilholinski receptor]]

== Reference ==
{{reflist|2}}

== Literatura ==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal  | author=Goyal RK  | last2=Underhill  | first2=Lisa H.  | last3=Goyal  | first3=Raj K. |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  }}
*{{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=10.1016/S0079-6123(08)62388-2  }}
*{{cite journal  | author=van Koppen CJ, Nathanson NM |title=Site-directed mutagenesis of the m2 muscarinic acetylcholine receptor. Analysis of the role of N-glycosylation in receptor expression and function. |journal=J. Biol. Chem. |volume=265 |issue= 34 |pages= 20887–92 |year= 1991 |pmid= 2249995 |doi=  }}
*{{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  | 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=10.1126/science.3037705  }}
*{{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=  | pmc=553870  }}
*{{cite journal  | author=Badner JA, Yoon SW, Turner G, ''et al.'' |title=Multipoint genetic linkage analysis of the m2 human muscarinic receptor gene. |journal=Mamm. Genome |volume=6 |issue= 7 |pages= 489–90 |year= 1995 |pmid= 7579899 |doi=10.1007/BF00360666  }}
*{{cite journal  | author=Offermanns S, Simon MI |title=G alpha 15 and G alpha 16 couple a wide variety of receptors to phospholipase C. |journal=J. Biol. Chem. |volume=270 |issue= 25 |pages= 15175–80 |year= 1995 |pmid= 7797501 |doi=10.1074/jbc.270.25.15175  }}
*{{cite journal  | author=Russell M, Winitz S, Johnson GL |title=Acetylcholine muscarinic m1 receptor regulation of cyclic AMP synthesis controls growth factor stimulation of Raf activity. | url=https://archive.org/details/sim_molecular-and-cellular-biology_1994-04_14_4/page/2343 |journal=Mol. Cell. Biol. |volume=14 |issue= 4 |pages= 2343–51 |year= 1994 |pmid= 8139539 |doi=  | pmc=358601  }}
*{{cite journal  | author=Kunapuli P, Onorato JJ, Hosey MM, Benovic JL |title=Expression, purification, and characterization of the G protein-coupled receptor kinase GRK5. |journal=J. Biol. Chem. |volume=269 |issue= 2 |pages= 1099–105 |year= 1994 |pmid= 8288567 |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=10.1074/jbc.271.5.2776  }}
*{{cite journal  | author=Kostenis E, Conklin BR, Wess J |title=Molecular basis of receptor/G protein coupling selectivity studied by coexpression of wild type and mutant m2 muscarinic receptors with mutant G alpha(q) subunits. |journal=Biochemistry |volume=36 |issue= 6 |pages= 1487–95 |year= 1997 |pmid= 9063897 |doi= 10.1021/bi962554d }}
*{{cite journal  | author=Smiley JF, Levey AI, Mesulam MM |title=Infracortical interstitial cells concurrently expressing m2-muscarinic receptors, acetylcholinesterase and nicotinamide adenine dinucleotide phosphate-diaphorase in the human and monkey cerebral cortex. |journal=Neuroscience |volume=84 |issue= 3 |pages= 755–69 |year= 1998 |pmid= 9579781 |doi=10.1016/S0306-4522(97)00524-1  }}
*{{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=10.1074/jbc.273.23.14538  }}
*{{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=10.1016/S0304-3940(99)00259-1  }}
*{{cite journal  | author=Retondaro FC, Dos Santos Costa PC, Pedrosa RC, Kurtenbach E |title=Presence of antibodies against the third intracellular loop of the m2 muscarinic receptor in the sera of chronic chagasic patients. | url=https://archive.org/details/sim_faseb-journal_1999-11_13_14/page/2015 |journal=FASEB J. |volume=13 |issue= 14 |pages= 2015–20 |year= 1999 |pmid= 10544184 |doi=  }}
*{{cite journal  | author=Waid DK, Chell M, El-Fakahany EE |title=M(2) and M(4) muscarinic receptor subtypes couple to activation of endothelial nitric oxide synthase. |journal=Pharmacology |volume=61 |issue= 1 |pages= 37–42 |year= 2000 |pmid= 10895079 |doi=10.1159/000028378  }}
*{{cite journal  | author=Obara K, Arai K, Miyajima N, ''et al.'' |title=Expression of m2 muscarinic acetylcholine receptor mRNA in primary culture of human prostate stromal cells. |journal=Urol. Res. |volume=28 |issue= 3 |pages= 196–200 |year= 2000 |pmid= 10929429 |doi=10.1007/s002400000113  }}
}}
* {{Cite book |ref= harv|author=Rang, H. P. |title=Pharmacology |url= https://archive.org/details/isbn_9788181479174|publisher=Churchill Livingstone |location=Edinburgh |year=2003 |isbn=0-443-07145-4 |oclc= |doi=}}
* {{Cite book |ref= harv|author=Boron, W. F and Boulpaep, E. L. |title=Medical Physiology |url= https://archive.org/details/medicalphysiolog0000boro|publisher=Elsevier Saunders |location=Philadelphia |year=2005 |pages=[https://archive.org/details/medicalphysiolog0000boro/page/387 387] |isbn=1-4160-2328-3 |oclc= |doi=}}
{{refend}}

== Spoljašnje veze ==
* {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2141 | title = Acetylcholine receptors (muscarinic): M<sub>2</sub> | accessdate =  | author =  | authorlink =  | coauthors =  | date =  | format =  | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | pages =  | language =  | archiveurl = https://web.archive.org/web/20150102105826/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2141 | archivedate = 2015-01-02 | quote =  | dead-url = yes }}
* {{MeshName|CHRM2+protein,+human}}
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{{DEFAULTSORT:Muskarinski acetilholinski receptor M2}}
[[Kategorija:G protein spregnuti receptori]]