Muscarinic acetylcholine receptor M3

Cholinergic receptor, muscarinic 3
Identifiers
Symbols CHRM3; HM3
External IDs OMIM: 118494 MGI: 88398 HomoloGene: 20191 IUPHAR: M3 GeneCards: CHRM3 Gene
Orthologs
Species Human Mouse
Entrez 1131 12671
Ensembl ENSG00000133019 ENSMUSG00000046159
UniProt P20309 Q542R4
RefSeq (mRNA) XM_001130695 NM_033269.4
RefSeq (protein) XP_001130695 NP_150372.1
Location (UCSC) Chr 1:
239.55 – 240.08 Mb		 Chr 13:
9.88 – 9.88 Mb
PubMed search [1] [2]

The muscarinic acetylcholine receptor M3, also known as the cholinergic receptor, muscarinic 3, is a muscarinic acetylcholine receptor. It is 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, as well as the lungs. They are also found in the CNS, where they induce emesis. In general, they cause smooth muscle contraction and increased glandular secretions.[1]

They are unresponsive to PTX and CTX.

Contents

Mechanism

Like the M1 muscarinic receptor, M3 receptors are coupled to G proteins of class Gq, which upregulate phospholipase C and, therefore, inositol trisphosphate and intracellular calcium as a signalling pathway. The calcium function in vertebrates also involves activation of protein kinase C and its effects.

Effects

Smooth muscle

Because the M3 receptor is Gq-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.[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:

Agonists

No highly selective M3 agonists are yet available as of 2009, but a number of non-selective muscarinic agonists are active at M3.

Antagonists

Interactions

Muscarinic acetylcholine receptor M3 has been shown to interact with Arf6[4] and ARF1.[4]

See also

References

  1. ^ a b "Entrez Gene: CHRM3 cholinergic receptor, muscarinic 3". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1131. 
  2. ^ 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. pp. page 185. ISBN 0-07-142280-3. 
  3. ^ a b c d e f g Rang HP, Dale MM, Ritter JM, Moore PK (2003). "Ch. 10". Pharmacology (5th ed.). Elsevier Churchill Livingstone. pp. page 139. ISBN 0-443-07145-4. 
  4. ^ a b Mitchell, Rory; Robertson Derek N, Holland Pamela J, Collins Daniel, Lutz Eve M, Johnson Melanie S (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

Further reading

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