Muskarinski acetilholinski receptor M2

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Muskarinski acetilholinski receptor M2‎‎
Identifikatori
Simboli CHRM2; FLJ43243; HM2; MGC120006; MGC120007
Vanjski ID OMIM118493 MGI88397 HomoloGene20190 IUPHAR: M2 GeneCards: CHRM2 Gene
Ortolozi
Vrsta Čovek Miš
Entrez 1129 243764
Ensembl ENSG00000181072 ENSMUSG00000045613
UniProt P08172 Q05CZ8
RefSeq (mRNA) NM_000739.2 NM_203491.3
RefSeq (protein) NP_000730.1 NP_987076.2
Lokacija (UCSC) Chr 7:
136.55 - 136.71 Mb
Chr 6:
36.34 - 36.48 Mb
PubMed pretraga [1] [2]

Muskarinski acetilholinski receptor M2 (holinergički receptor, muskarinski 2) je muskarinski acetilholinski receptor.

Funkcija[uredi - уреди]

Srce[uredi - уреди]

M2 muskarinski receptori su locirani u srcu, gde usporavaju brzinu srca do normalnog sinusnog ritma nakon stimulatornog dejstva simpatetičkog nervnog sistema, putem usporavanja brzine depolarizacije. Oni takođe redukuju kontraktilne sile atrijalnog srčanog mišića, i umanjuju provodnu brzinu atrioventrikularnog čvora (AV čvor). Oni nemaju efekta na kontrakcione sile ventrikularnog mišića.

IQ[uredi - уреди]

Jedna danska porodična studija iz 2006 je utvrdila da postoji "veoma značajna veze" između CHRM2 gena i inteligencije. Ova studija je koristila uzorak od 667 osoba iz 304 porodice.[1] Slična veza je nezavisno nađena u studiji blizanaca i porodica u Minesoti.[2] Međutim, kasniji pokušaji iz 2009. da se potvrde ove tvrdnje je bili neuspešni.[3]

Mehanizam[uredi - уреди]

M2 muskarinski receptori deluju putem Gi tipa receptora, koji uzrokuju smanjenje cAMP koncentracije u ćeliji, generalno dovodeći do inhibitornih efekata.

Oni takođe moduliraju muskarinske kalijumove kanale.[4][5] U srcu, oni doprinose smanjenju brzine rada srca.

Gen[uredi - уреди]

Muskarinski acetilholinski receptor M2 je kodiran genom CHRM2.[6] Višestruke alternativno splajsovane transkriptne varijante ovog gene au nađene.[6]

Ligandi[uredi - уреди]

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

Agonisti[uredi - уреди]

  • 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 M2 agonist)[7]

Antagonisti[uredi - уреди]

  • 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

Vidi još[uredi - уреди]

Reference[uredi - уреди]

  1. Gosso MF, van Belzen M, de Geus EJ, et al. (2006). "Association between the CHRM2 gene and intelligence in a sample of 304 Dutch families". Genes, Brain and Behavior 5 (8 pages=577–584). doi:10.1111/j.1601-183X.2006.00211.x. PMID 17081262. 
  2. Dick DM, Aliev F, Kramer J, et al. (2007). "Association of CHRM2 with IQ: converging evidence for a gene influencing intelligence". Behav. Genet. 37 (2): 265–272. doi:10.1007/s10519-006-9131-2. PMID 17160701. 
  3. Lind PA, Luciano M, Horan MA, et al. (September 2009). "No association between Cholinergic Muscarinic Receptor 2 (CHRM2) genetic variation and cognitive abilities in three independent samples". Behav. Genet. 39 (5): 513–23. doi:10.1007/s10519-009-9274-z. PMID 19418213. 
  4. Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. 
  5. Boron, W. F and Boulpaep, E. L. (2005). Medical Physiology. Philadelphia: Elsevier Saunders. str. 387. ISBN 1-4160-2328-3. 
  6. 6.0 6.1 "Entrez Gene: CHRM2 cholinergic receptor, muscarinic 2". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1129. 
  7. 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 (March 2006). "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". J. Med. Chem. 49 (6): 1925–31. doi:10.1021/jm0510878. PMID 16539379. 

Literatura[uredi - уреди]

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  • Brann MR, Ellis J, Jørgensen H, et al. (1994). "Muscarinic acetylcholine receptor subtypes: localization and structure/function.". Prog. Brain Res. 98: 121–7. doi:10.1016/S0079-6123(08)62388-2. PMID 8248499. 
  • van Koppen CJ, Nathanson NM (1991). "Site-directed mutagenesis of the m2 muscarinic acetylcholine receptor. Analysis of the role of N-glycosylation in receptor expression and function.". J. Biol. Chem. 265 (34): 20887–92. PMID 2249995. 
  • 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. PMID 2739737. 
  • 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. PMID 3037705. 
  • Peralta EG, Ashkenazi A, Winslow JW, et al. (1988). "Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors.". EMBO J. 6 (13): 3923–9. PMC 553870. PMID 3443095. 
  • Badner JA, Yoon SW, Turner G, et al. (1995). "Multipoint genetic linkage analysis of the m2 human muscarinic receptor gene.". Mamm. Genome 6 (7): 489–90. doi:10.1007/BF00360666. PMID 7579899. 
  • Offermanns S, Simon MI (1995). "G alpha 15 and G alpha 16 couple a wide variety of receptors to phospholipase C.". J. Biol. Chem. 270 (25): 15175–80. doi:10.1074/jbc.270.25.15175. PMID 7797501. 
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  • Kunapuli P, Onorato JJ, Hosey MM, Benovic JL (1994). "Expression, purification, and characterization of the G protein-coupled receptor kinase GRK5.". J. Biol. Chem. 269 (2): 1099–105. PMID 8288567. 
  • Haga K, Kameyama K, Haga T, et al. (1996). "Phosphorylation of human m1 muscarinic acetylcholine receptors by G protein-coupled receptor kinase 2 and protein kinase C.". J. Biol. Chem. 271 (5): 2776–82. doi:10.1074/jbc.271.5.2776. PMID 8576254. 
  • Kostenis E, Conklin BR, Wess J (1997). "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.". Biochemistry 36 (6): 1487–95. doi:10.1021/bi962554d. PMID 9063897. 
  • Smiley JF, Levey AI, Mesulam MM (1998). "Infracortical interstitial cells concurrently expressing m2-muscarinic receptors, acetylcholinesterase and nicotinamide adenine dinucleotide phosphate-diaphorase in the human and monkey cerebral cortex.". Neuroscience 84 (3): 755–69. doi:10.1016/S0306-4522(97)00524-1. PMID 9579781. 
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  • Sato KZ, Fujii T, Watanabe Y, et al. (1999). "Diversity of mRNA expression for muscarinic acetylcholine receptor subtypes and neuronal nicotinic acetylcholine receptor subunits in human mononuclear leukocytes and leukemic cell lines.". Neurosci. Lett. 266 (1): 17–20. doi:10.1016/S0304-3940(99)00259-1. PMID 10336173. 
  • Retondaro FC, Dos Santos Costa PC, Pedrosa RC, Kurtenbach E (1999). "Presence of antibodies against the third intracellular loop of the m2 muscarinic receptor in the sera of chronic chagasic patients.". FASEB J. 13 (14): 2015–20. PMID 10544184. 
  • Waid DK, Chell M, El-Fakahany EE (2000). "M(2) and M(4) muscarinic receptor subtypes couple to activation of endothelial nitric oxide synthase.". Pharmacology 61 (1): 37–42. doi:10.1159/000028378. PMID 10895079. 
  • Obara K, Arai K, Miyajima N, et al. (2000). "Expression of m2 muscarinic acetylcholine receptor mRNA in primary culture of human prostate stromal cells.". Urol. Res. 28 (3): 196–200. doi:10.1007/s002400000113. PMID 10929429. 
  • Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. 
  • Boron, W. F and Boulpaep, E. L. (2005). Medical Physiology. Philadelphia: Elsevier Saunders. str. 387. ISBN 1-4160-2328-3. 

Spoljašnje veze[uredi - уреди]