Muskarinski acetilholinski receptor M4
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Muskarinski acetilholinski receptor M4 (muskarinski holinergijski receptor 4, CHRM4), je protein koji je kod ljudi kodiran CHRM4 genom.[1][2]
Funkcije[uredi | uredi kod]
Muskarinski acetilholinski receptori pripadaju velikoj familiji G protein spregnutih receptora. Funkcionalna raznovrsnost ovih receptora je definisana vezivanjem acetilholina, i obuhvata ćelijske odgovore poput inhibicije adenilat ciklaze, fosfoinozitidne degeneracije i modulacije kalijumovih kanala. Muskarinski receptori posreduju mnoge efekte acetilholina u centralnom i perifernom nervnom sistemu. Klinički značaj ovoj receptora nije poznat; međutim, studije na miševima su ustanovile vezu između njegovog dejstva i inhibicije adenilil ciklaze.[1]
M4 muskarinski receptori deluju kao inhibitorni autoreceptori za acetilholin. Aktivacija M4 receptora inhibira oslobađanje acetilholina u striatumu. M2 podtip acetilholinksog receptora deluje na sličan način, kao inhibitorni autoreceptor acetilholinskog otpuštanja, mada taj receptor deluje prvenstveno u hipokampusu i cerebralnom korteksu.
Muskarinski acetilholinski receptori imaju regulatorno dejstvo na dopaminergijsku neurotransmisiju. Aktivacija M4 receptora u striatumu inhibira D1-indukovanu lokomotornu stimulaciju kod miševa. Miševi koji su deficitarni u M4 receptorima ispoljavaju povećanu lokomotornu stimulaciju u odgovoru na D1 agoniste, amfetamin i kokain.[3][4][5] Neurotransmisija u striatumu utiče na ekstrapiramidalnu motornu kontrolu, tako da alteracije M4 aktivnosti mogu da doprinosu oboljenjima poput Parkinsonove bolesti.[6][7][8]
Ligandi[uredi | uredi kod]
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Reference[uredi | uredi kod]
- ↑ 1,0 1,1 „Entrez Gene: CHRM4 cholinergic receptor, muscarinic 4”.
- ↑ Grewal RP, Martinez M, Hoehe M, Bonner TI, Gershon ES, Detera-Wadleigh S (May 1992). „Genetic linkage mapping of the m4 human muscarinic receptor (CHRM4)”. Genomics 13 (1): 239–40. DOI:10.1016/0888-7543(92)90236-L. PMID 1577490.
- ↑ Gomeza J, Zhang L, Kostenis E, Felder C, Bymaster F, Brodkin J, Shannon H, Xia B, Deng C, Wess J (August 1999). „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. PMC 17915. PMID 10468635.
- ↑ Jeon J, Dencker D, Wörtwein G, et al. (February 2010). „A subpopulation of neuronal M4 muscarinic acetylcholine receptors plays a critical role in modulating dopamine-dependent behaviors”. J. Neurosci. 30 (6): 2396–405. DOI:10.1523/JNEUROSCI.3843-09.2010. PMC 2824442. PMID 20147565.
- ↑ Schmidt L. S., Thomsen M., Weikop P., Dencker D., Wess J. R., Woldbye D. P. D., Wortwein G., Fink-Jensen A. (2011). „Increased cocaine self-administration in M4 muscarinic acetylcholine receptor knockout mice”. Psychopharmacology 216 (3): 367–378. DOI:10.1007/s00213-011-2225-4. PMID 21373792.
- ↑ Langmead CJ, Watson J, Reavill C (February 2008). „Muscarinic acetylcholine receptors as CNS drug targets”. Pharmacology & Therapeutics 117 (2): 232–43. DOI:10.1016/j.pharmthera.2007.09.009. PMID 18082893.
- ↑ Stein IS, Hell JW (June 2010). „CaMKII hunkers down on the muscarinic M4 receptor to help curb cocaine-induced hyperlocomotion”. The EMBO Journal 29 (12): 1943–5. DOI:10.1038/emboj.2010.105. PMC 2892364. PMID 20551968.
- ↑ Guo ML, Mao LM, Wang JQ (December 2010). „Modulation of M4 muscarinic acetylcholine receptors by interacting proteins”. Neuroscience Bulletin 26 (6): 469–73. PMC 3139403. PMID 21113197.
- ↑ Chan WY, McKinzie DL, Bose S, et al. (2008). „Allosteric modulation of the muscarinic M4 receptor as an approach to treating schizophrenia”. PNAS 105 (31): 10978–83. DOI:10.1073/pnas.0800567105. PMC 2495016. PMID 18678919.
- ↑ Brady AE, Jones CK, Bridges TM, et al. (2008). „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. DOI:10.1124/jpet.108.140350. PMC 2745822. PMID 18772318.
- ↑ Teaktong T, Piggott MA, Mckeith IG, Perry RH, Ballard CG, Perry EK (June 2005). „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. DOI:10.1016/j.bbr.2005.02.019. PMID 15922057.
- ↑ Muscarinic toxin 3, Dendroaspis angusticeps (Eastern green mamba)
- ↑ Lazareno S, Buckley NJ, Roberts FF (December 1990). „Characterization of muscarinic M4 binding sites in rabbit lung, chicken heart, and NG108-15 cells”. Molecular Pharmacology 38 (6): 805–15. PMID 2250662.
Literatura[uredi | uredi kod]
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- Grewal RP, Martinez M, Hoehe M, et al. (1992). „Genetic linkage mapping of the m4 human muscarinic receptor (CHRM4).”. Genomics 13 (1): 239–40. DOI:10.1016/0888-7543(92)90236-L. PMID 1577490.
- Detera-Wadleigh SD, Wiesch D, Bonner TI (1989). „An SstI polymorphism for the human muscarinic acetylcholine receptor gene, m4 (CHRM 4).”. Nucleic Acids Res. 17 (15): 6431. DOI:10.1093/nar/17.15.6431. PMC 318330. PMID 2570410.
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- 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.
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