Muscarinic acetylcholine receptor M2

Cholinergic receptor, muscarinic 2
Identifiers
Symbols CHRM2; FLJ43243; HM2; MGC120006; MGC120007
External IDs OMIM: 118493 MGI: 88397 HomoloGene: 20190 IUPHAR: M2 GeneCards: CHRM2 Gene
Orthologs
Species Human Mouse
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
Location (UCSC) Chr 7:
136.55 – 136.71 Mb		 Chr 6:
36.34 – 36.48 Mb
PubMed search [1] [2]

The muscarinic acetylcholine receptor M2, also known as the cholinergic receptor, muscarinic 2, is a muscarinic acetylcholine receptor.

Contents

Function

Heart

The M2 muscarinic receptors are located in the heart, where they act to slow the heart rate down to normal sinus rhythm after stimulatory actions of the sympathetic nervous system, by slowing the speed of depolarization. They also reduce contractile forces of the atrial cardiac muscle, and reduce conduction velocity of the atrioventricular node (AV node). However, they have no effect on the contractile forces of the ventricular muscle.

IQ

A 2006 Dutch family study found that there is "a highly significant association" between the CHRM2 gene and intelligence. The study concluded that there was an association between the CHRM2 gene on chromosome 7 and Performance IQ, as measured by the Wechsler Adult Intelligence Scale-Revised. The Dutch family study used a sample of 667 individuals from 304 families.[1] A similar association was found independently in the Minnesota Twin and Family Study (Comings et al. 2003) and by the Department of Psychiatry at the Washington University.[2] However, a larger 2009 study attempting to replicate this claim instead found no significant association between the CHRM2 gene and intelligence in a Scottish cohort of 2,091 individuals over age 50, nor an English sample of 758 non-cognitively-impaired elderly individuals, nor an Australian family-based sample of 1,537 adolescents.[3]

Mechanism

M2 muscarinic receptors act via a Gi type receptor, which causes a decrease in cAMP in the cell, generally leading to inhibitory-type effects.

In addition, they modulate muscarinic potassium channels.[4][5] In the heart, this contributes to a decreased heart rate.

Gene

Muscarinic acetylcholine receptor M2 is encoded by the gene CHRM2.[6]

Multiple alternatively spliced transcript variants have been described for this gene.[6]

Ligands

Few highly selective M2 agonists are available at present, although there are several non-selective muscarinic agonists that stimulate M2, and a number of selective M2 antagonists are available.

Agonists

Antagonists

See also

References

  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): 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. pp. 387. ISBN 1-4160-2328-3. 
  6. ^ a b "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. 

Further reading

External links

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