Muskarinski acetilholinski receptor M2

Izvor: Wikipedia
edit
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]

  • Goyal RK; Underhill, Lisa H.; Goyal, Raj K. (1989). "Muscarinic receptor subtypes. Physiology and clinical implications.". N. Engl. J. Med. 321 (15): 1022–9. doi:10.1056/NEJM198910123211506. PMID 2674717. 
  • 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. 
  • Russell M, Winitz S, Johnson GL (1994). "Acetylcholine muscarinic m1 receptor regulation of cyclic AMP synthesis controls growth factor stimulation of Raf activity.". Mol. Cell. Biol. 14 (4): 2343–51. PMC 358601. PMID 8139539. 
  • 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. 
  • von der Kammer H, Mayhaus M, Albrecht C et al. (1998). "Muscarinic acetylcholine receptors activate expression of the EGR gene family of transcription factors.". J. Biol. Chem. 273 (23): 14538–44. doi:10.1074/jbc.273.23.14538. PMID 9603968. 
  • 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]