Biology:Muscarinic acetylcholine receptor M4
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Short description: Protein-coding gene
 Generic protein structure example |
The muscarinic acetylcholine receptor M4, also known as the cholinergic receptor, muscarinic 4 (CHRM4), is a protein that, in humans, is encoded by the CHRM4 gene.[1][2]
Function
M4 muscarinic receptors are coupled to Gi/o heterotrimeric proteins.[3]
They function as inhibitory autoreceptors for acetylcholine. Activation of M4 receptors inhibits acetylcholine release in the striatum. The M2 subtype of acetylcholine receptor functions similarly as an inhibitory autoreceptor to acetylcholine release, albeit functioning actively primarily in the hippocampus and cerebral cortex.
Muscarinic acetylcholine receptors possess a regulatory effect on dopaminergic neurotransmission. Activation of M4 receptors in the striatum inhibit D1-induced locomotor stimulation in mice. M4 receptor-deficient mice exhibit increased locomotor simulation in response to D1 agonists, amphetamine and cocaine.[4][5][6] Neurotransmission in the striatum influences extrapyramidal motor control, thus alterations in M4 activity may contribute to conditions such as Parkinson's disease.[7][8][9]
Ligands
Orthosteric agonists
Positive allosteric modulators
Antagonists
- AFDX-384 (mixed M2/M4 antagonist, N-[2-[2-[(Dipropylamino)methyl]-1-piperidinyl]ethyl]-5,6-dihydro-6-oxo-11H-pyrido[2,3-b][1,4]benzodiazepine-11-carboxamide, CAS# 118290-27-0)
- Dicycloverine[17]
- Himbacine
- Mamba toxin 3[18]
- PD-102,807 (3,6a,11,14-Tetrahydro-9-methoxy-2-methyl-(12H)-isoquino[1,2-b]pyrrolo[3,2-f][1,3]benzoxazine-1-carboxylic acid ethyl ester, CAS# 23062-91-1)
- PD-0298029
- Tropicamide - moderate selectivity over other muscarinic subtypes (2-5x approx)[19]
- Diphenhydramine
See also
References
- ↑ "Entrez Gene: CHRM4 cholinergic receptor, muscarinic 4". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1132.
- ↑ "Genetic linkage mapping of the m4 human muscarinic receptor (CHRM4)". Genomics 13 (1): 239–40. May 1992. doi:10.1016/0888-7543(92)90236-L. PMID 1577490. https://zenodo.org/record/1258587.
- ↑ "Inactive-state preassembly of G(q)-coupled receptors and G(q) heterotrimers". Nat. Chem. Biol. 7 (10): 740–7. 2011. doi:10.1038/nchembio.642. PMID 21873996.
- ↑ "Enhancement of D1 dopamine receptor-mediated locomotor stimulation in M(4) muscarinic acetylcholine receptor knockout mice". Proceedings of the National Academy of Sciences of the United States of America 96 (18): 10483–8. August 1999. doi:10.1073/pnas.96.18.10483. PMID 10468635. Bibcode: 1999PNAS...9610483G.
- ↑ "A subpopulation of neuronal M4 muscarinic acetylcholine receptors plays a critical role in modulating dopamine-dependent behaviors". J. Neurosci. 30 (6): 2396–405. February 2010. doi:10.1523/JNEUROSCI.3843-09.2010. PMID 20147565.
- ↑ "Increased cocaine self-administration in M4 muscarinic acetylcholine receptor knockout mice". Psychopharmacology 216 (3): 367–378. 2011. doi:10.1007/s00213-011-2225-4. PMID 21373792.
- ↑ "Muscarinic acetylcholine receptors as CNS drug targets". Pharmacology & Therapeutics 117 (2): 232–43. February 2008. doi:10.1016/j.pharmthera.2007.09.009. PMID 18082893.
- ↑ "CaMKII hunkers down on the muscarinic M4 receptor to help curb cocaine-induced hyperlocomotion". The EMBO Journal 29 (12): 1943–5. June 2010. doi:10.1038/emboj.2010.105. PMID 20551968.
- ↑ "Modulation of M4 muscarinic acetylcholine receptors by interacting proteins". Neuroscience Bulletin 26 (6): 469–73. December 2010. doi:10.1007/s12264-010-0933-0. PMID 21113197.
- ↑ "Allosteric modulation of the muscarinic M4 receptor as an approach to treating schizophrenia". PNAS 105 (31): 10978–83. 2008. doi:10.1073/pnas.0800567105. PMID 18678919. Bibcode: 2008PNAS..10510978C.
- ↑ 11.0 11.1 "Centrally active allosteric potentiators of the M4 muscarinic acetylcholine receptor reverse amphetamine-induced hyperlocomotor activity in rats". J. Pharmacol. Exp. Ther. 327 (3): 941–53. 2008. doi:10.1124/jpet.108.140350. PMID 18772318.
- ↑ "An allosteric enhancer of M4 muscarinic acetylcholine receptor function inhibits behavioral and neurochemical effects of cocaine". Psychopharmacology 224 (2): 277–87. 2012. doi:10.1007/s00213-012-2751-8. PMID 22648127.
- ↑ "Antipsychotic drug-like effects of the selective M4 muscarinic acetylcholine receptor positive allosteric modulator VU0152100". Neuropsychopharmacology 39 (7): 1578–93. 2014. doi:10.1038/npp.2014.2. PMID 24442096.
- ↑ "Effects of selective activation of M1 and M4 muscarinic receptors on object recognition memory performance in rats". Pharmacology 93 (1–2): 57–64. 2014. doi:10.1159/000357682. PMID 24480931.
- ↑ "M4 mAChR-mediated modulation of glutamatergic transmission at corticostriatal synapses". ACS Chem Neurosci 5 (4): 318–24. 2014. doi:10.1021/cn500003z. PMID 24528004.
- ↑ "Probing structural requirements of positive allosteric modulators of the M4 muscarinic receptor". J. Med. Chem. 56 (20): 8196–200. 2013. doi:10.1021/jm401032k. PMID 24074052.
- ↑ "Muscarinic M2 and M4 receptors in anterior cingulate cortex: relation to neuropsychiatric symptoms in dementia with Lewy bodies". Behavioural Brain Research 161 (2): 299–305. June 2005. doi:10.1016/j.bbr.2005.02.019. PMID 15922057.
- ↑ "Muscarinic toxin 3 - Dendroaspis angusticeps (Eastern green mamba)". https://www.uniprot.org/uniprot/P81031.
- ↑ "Characterization of muscarinic M4 binding sites in rabbit lung, chicken heart, and NG108-15 cells". Molecular Pharmacology 38 (6): 805–15. December 1990. PMID 2250662.
Further reading
- Goyal RK (1989). "Muscarinic receptor subtypes. Physiology and clinical implications". N. Engl. J. Med. 321 (15): 1022–9. doi:10.1056/NEJM198910123211506. PMID 2674717.
- "Muscarinic acetylcholine receptor subtypes: localization and structure/function". Prog. Brain Res. 98: 121–7. 1993. doi:10.1016/S0079-6123(08)62388-2. PMID 8248499.
- "Genetic linkage mapping of the m4 human muscarinic receptor (CHRM4)". Genomics 13 (1): 239–40. 1992. doi:10.1016/0888-7543(92)90236-L. PMID 1577490. https://zenodo.org/record/1258587.
- "An SstI polymorphism for the human muscarinic acetylcholine receptor gene, m4 (CHRM 4).". Nucleic Acids Res. 17 (15): 6431. 1989. doi:10.1093/nar/17.15.6431. PMID 2570410.
- "Acetylcholine analogue stimulates DNA synthesis in brain-derived cells via specific muscarinic receptor subtypes.". Nature 340 (6229): 146–50. 1989. doi:10.1038/340146a0. PMID 2739737. Bibcode: 1989Natur.340..146A.
- "Identification of a family of muscarinic acetylcholine receptor genes.". Science 237 (4814): 527–32. 1987. doi:10.1126/science.3037705. PMID 3037705. Bibcode: 1987Sci...237..527B. https://zenodo.org/record/1231199.
- "Cloning and expression of the human and rat m5 muscarinic acetylcholine receptor genes.". Neuron 1 (5): 403–10. 1990. doi:10.1016/0896-6273(88)90190-0. PMID 3272174.
- "Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors.". EMBO J. 6 (13): 3923–9. 1988. doi:10.1002/j.1460-2075.1987.tb02733.x. PMID 3443095.
- "Isolation, sequence and functional expression of the mouse m4 muscarinic acetylcholine receptor gene.". Biochim. Biophys. Acta 1173 (3): 342–4. 1993. doi:10.1016/0167-4781(93)90135-z. PMID 7916637.
- "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. 1996. doi:10.1074/jbc.271.5.2776. PMID 8576254.
- "Muscarinic acetylcholine receptors activate expression of the EGR gene family of transcription factors.". J. Biol. Chem. 273 (23): 14538–44. 1998. doi:10.1074/jbc.273.23.14538. PMID 9603968.
- "SH3 binding domains in the dopamine D4 receptor.". Biochemistry 37 (45): 15726–36. 1998. doi:10.1021/bi981634+. PMID 9843378. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape9/PQDD_0017/NQ45764.pdf.
- "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. 1999. doi:10.1016/S0304-3940(99)00259-1. PMID 10336173.
- "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags.". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3491–6. 2000. doi:10.1073/pnas.97.7.3491. PMID 10737800. Bibcode: 2000PNAS...97.3491D.
- "Expression of multiple subtypes of muscarinic receptors and cellular distribution in the human heart.". Mol. Pharmacol. 59 (5): 1029–36. 2001. doi:10.1124/mol.59.5.1029. PMID 11306684.
- "Identification and characterization of muscarinic acetylcholine receptor subtypes expressed in human skin melanocytes.". Mol. Cell. Biochem. 228 (1–2): 57–72. 2002. doi:10.1023/A:1013368509855. PMID 11855742.
- "Novel interaction between the M4 muscarinic acetylcholine receptor and elongation factor 1A2". J. Biol. Chem. 277 (32): 29268–74. 2002. doi:10.1074/jbc.M203081200. PMID 12048193.
- "Decreased muscarinic1 receptors in the dorsolateral prefrontal cortex of subjects with schizophrenia". Mol. Psychiatry 7 (10): 1083–91. 2003. doi:10.1038/sj.mp.4001199. PMID 12476323.
External links
- Overview of all the structural information available in the PDB for UniProt: P08173 (Muscarinic acetylcholine receptor M4) at the PDBe-KB.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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