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muscarinic M3 receptor; muscarinic acetylcholine receptor M3 (CHRM3)
Function:
1) activates Gq proteins
2) stimulates phosphoinositide hydrolysis & Ca+2 mobilization
3) involved in pancreatic endocrine & exocrine secretion [1]
4) involved in bladder smooth muscle contraction [4,6]
Structure: belongs to the G-protein coupled receptor 1 family
Compartment:
- cell membrane, cell junction, synapse
- postsynaptic cell membrane
- basolateral cell membrane
Expression:
- expressed in smooth muscle, GI tract, urinary bladder, myocardium [5,6]
Pharmacology:
- muscarinic M3 receptor specific antagonists (solifenacin & darifenacin) have been developed to specifically antagonize detrussor hyperactivity associated with urge incontinence
Interactions
molecular events
General
muscarinic receptor
Properties
SIZE: entity length = 590 aa
MW = 66 kD
COMPARTMENT: synaptic membrane
CELL: neuron
MOTIF: exoplasmic domain {1-67}
MOTIF: N-glycosylation site {N5}
N-glycosylation site {N6}
N-glycosylation site {N15}
N-glycosylation site {N41}
N-glycosylation site {N48}
transmembrane domain {68-91}
cytoplasmic domain {92-104}
transmembrane domain {105-125}
exoplasmic domain {126-142}
MOTIF: cysteine residue {C141}
MODIFICATION: cysteine residue {C221}
transmembrane domain {143-164}
cytoplasmic domain {165-184}
transmembrane domain {185-207}
exoplasmic domain {208-229}
MOTIF: cysteine residue {C221}
MODIFICATION: cysteine residue {C141}
transmembrane domain {230-252}
cytoplasmic domain {253-492}
transmembrane domain {493-513}
exoplasmic domain {514-527}
transmembrane domain {528-547}
cytoplasmic domain {548-590}
MISC-INFO: Ki [PIRENZEPINE] LOW
INHIBITOR = PFHHSID
INHIBITOR = HHSID
INHIBITOR = DARIFENACIN
Database Correlations
OMIM 118494
UniProt P20309
Pfam PF00001
Entrez Gene 1131
Kegg hsa:1131
References
- Conkilin et al PNAS 85:8698 (1988)
- Entrez Gene :accession 1131
- Mukerji G et al,
Localization of M2 and M3 muscarininc receptors in human
bladder disorders and their clinical correlations.
J Urol. 2006, 176:367
PMID: 16753445
- Gromada J & Hughes TE
Ringing the dinner bell for insulin: muscarinic M3 receptor
activity in the control of pancreatic beta cell function.
Cell Metab. 2006, 3:390
PMID: 16753574
- Wang Z et al
Functional M3 muscarinic acetylcholine receptors in mammalian
hearts
Br J Pharmacol 2004, 142:395
PMID: 15148264
- Ehlert FJ
Pharmacologic analysis of the contractile role of M2 and M3
muscarinic receptors in smooth muscle.
Receptors Channels 2003, 9:261
PMID: 12893538
- Kruse AC et al
Structure and dynamics of the M3 muscarinic acetylcholine
receptor.
Nature. 2012 Feb 22;482(7386):552-6. doi: 10.1038/nature10867.
PMID: 22358844