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Muskarinski acetilholinski receptor M1‎‎
Muskarinski acetilholinski receptor M1‎‎
Identifikatori
Simboli	CHRM1; HM1; M1; M1R; MGC30125
Vanjski ID	OMIM: 118510 MGI: 88396 HomoloGene: 20189 IUPHAR: M1 GeneCards: CHRM1 Gene
Ontologija gena
Molekularna funkcija	• aktivnost fosfatidilinozitol fosfolipaze C; • aktivnost receptora; • aktivnost G-protein spregnutog receptora; • aktivnost muskarinskog acetilholinskog receptora; • vezivane proteina; • vezivanje lekova;
Celularna komponenta	• membranska frakcija; • ćelijska membran; • integralno sa ćelijskom membranom; • postsinaptička gustina; • ćelijski spoj; • dendrit; • asimetrična sinapsa; • aksonski terminus; • postsinaptička membrana;
Biološki proces	• proces modifikacije proteina; • prenos signala; • signalni put G-protein spregnutog receptora; • aktivacija protein kinaze C; • aktivacija aktivnosti fosfolipaze C signalnim putem muskarinskog acetilholinskog receptora; • signalni put muskarinskog acetilholinskog receptora; • neuromaskularna sinaptička transmisija; • razvoj nervnog sistema; • ćelijska proliferacija; • pozitivna regulacija ćelijske proliferacije; • regulacija kretanja;
Ortolozi
Vrsta	Čovek
Entrez	1128
Ensembl	ENSG00000168539
UniProt	P11229
RefSeq (mRNA)	NM_000738
RefSeq (protein)	NP_000729
Lokacija (UCSC)	Chr 11:; 62.68 - 62.69 Mb
PubMed pretraga	[1]

Muskarinski acetilholinski receptor M₁ (holinergički receptor, muskarinski 1) je muskarinski receptor.

Za ovaj receptor je nađeno da posreduje spori ekscitatorni postsinaptički potencijal u ganglionima postganglionskim nervima.^[1] On je visoko zastupljen u eksokrinim žlezdama i u CNS-u.^[2]^[3]

On se predominantno vezuje za G_q klasu G proteina,^[4] koja stimuliše dejstvo fosfolipaze C i stoga inozitol trisfosfata i signalnog puta intracelularnog kalcijuma.

Efekti

EPSP u autonomnom ganglionu
sekrecija iz pljuvačnih žlezdi
sekrecija želudačne kiseline u želucu^[5]
CNS (memorija)^[6]
vagalno indukovana bronhokonstrikcija^[5]

Mehanizam

On formira spregu sa G_q, i u manjoj meri G_i i G_s. To dovodi do sporog EPSP i umanjene K⁺ provodnosti.^[6]^[7]

Ligandi

=== Agonisti ===

acetilholin
karbahol^[6]
CDD-0097
McN-A-343 - mešoviti M1/M4 agonist^[6]
L-689,660 - mešoviti M1/M3 agonist
Oksotremorin
Vedaklidin
Ksanomelin
Muskarin
77-LH-28-1 selektivni M₁ alosterni agonist

Alosterni modulatori

benzilhinolon karboksilna kiselina^[8]
VU-0090157^[9]
VU-0029767^[9]

Antagonisti

atropin^[6]
dicikloverin^[6]
tolterodin^[6]
oksibutinin^[6]
ipratropijum^[6]
mamba toksin muskarinski toksin 7 (MT7)^[6]
pirenzepin
telenzepin

Gen

Ovaj receptor je kodiran humanim genom CHRM1.^[5] On se nalazi na 11q13.^[5]

Vidi još

Muskarinski acetilholinski receptor

Reference

^ Messer, Jr, WS (20. 1. 2000). „Acetylcholine”. University of Toledo. Архивирано из оригинала 14. 10. 2007. г. Приступљено 27. 10. 2007.
^ Johnson, Gordon (2002). PDQ Pharmacology (2nd изд.). Hamilton, Ontario: BC Decker Inc. стр. 311 pages. ISBN 1-55009-109-3.
^ Richelson, Elliott (2000). „Cholinergic Transduction, Psychopharmacology - The Fourth Generation of Progress”. American College of Neuropsychopharmacology. Приступљено 27. 10. 2007.
^ Burford NT, Nahorski SR (1996). „Muscarinic m1 receptor-stimulated adenylate cyclase activity in Chinese hamster ovary cells is mediated by Gs alpha and is not a consequence of phosphoinositidase C activation”. Biochem. J. 315 (Pt 3): 883—8. PMC 1217289 . PMID 8645172.
^ ^а ^б ^в ^г „Entrez Gene: CHRM1 cholinergic receptor, muscarinic 1”.
^ ^а ^б ^в ^г ^д ^ђ ^е ^ж ^з ^и Rang HP, Dale MM, Ritter JM, Moore PK (2003). „10”. Pharmacology (5th изд.). Elsevier Churchill Livingstone. стр. 139. ISBN 0-443-07145-4.
^ Uchimura N, North RA (1. 3. 1990). „Muscarine reduces inwardly rectifying potassium conductance in rat nucleus accumbens neurones”. J. Physiol. (Lond.). 422 (1): 369—80. PMC 1190137 . PMID 1693682.
^ Shirey JK, Brady AE, Jones PJ, Davis AA, Bridges TM, Kennedy JP, Jadhav SB, Menon UN, Xiang Z, Watson ML, Christian EP, Doherty JJ, Quirk MC, Snyder DH, Lah JJ, Levey AI, Nicolle MM, Lindsley CW, Conn PJ (2009). „A selective allosteric potentiator of the M1 muscarinic acetylcholine receptor increases activity of medial prefrontal cortical neurons and restores impairments in reversal learning”. J. Neurosci. 29 (45): 14271—86. PMC 2811323 . PMID 19906975. doi:10.1523/JNEUROSCI.3930-09.2009.
^ ^а ^б Marlo JE; Niswender CM; Days EL; et al. (2008). „Discovery and characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity”. Mol. Pharmacol. 75 (3): 577—88. PMC 2684909 . PMID 19047481. doi:10.1124/mol.108.052886.

Literatura

Rang HP, Dale MM, Ritter JM, Moore PK (2003). „10”. Pharmacology (5th изд.). Elsevier Churchill Livingstone. стр. 139. ISBN 0-443-07145-4.
Johnson, Gordon (2002). PDQ Pharmacology (2nd изд.). Hamilton, Ontario: BC Decker Inc. стр. 311 pages. ISBN 1-55009-109-3.

Goyal RK; Underhill, Lisa H.; Goyal, Raj K. (1989). „Muscarinic receptor subtypes. Physiology and clinical implications.”. N. Engl. J. Med. 321 (15): 1022—9. PMID 2674717. doi:10.1056/NEJM198910123211506.
Brann MR; Ellis J; Jørgensen H; et al. (1994). „Muscarinic acetylcholine receptor subtypes: localization and structure/function.”. Prog. Brain Res. 98: 121—7. PMID 8248499. doi:10.1016/S0079-6123(08)62388-2.
Nitsch RM, Slack BE, Wurtman RJ, Growdon JH (1992). „Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors.”. Science. 258 (5080): 304—7. PMID 1411529. doi:10.1126/science.1411529.
Arden JR; Nagata O; Shockley MS; et al. (1992). „Mutational analysis of third cytoplasmic loop domains in G-protein coupling of the HM1 muscarinic receptor.”. Biochem. Biophys. Res. Commun. 188 (3): 1111—5. PMID 1445347. doi:10.1016/0006-291X(92)91346-R.
Gutkind JS, Novotny EA, Brann MR, Robbins KC (1991). „Muscarinic acetylcholine receptor subtypes as agonist-dependent oncogenes.”. Proc. Natl. Acad. Sci. U.S.A. 88 (11): 4703—7. PMC 51734 . PMID 1905013. doi:10.1073/pnas.88.11.4703.
Chapman CG, Browne MJ (1990). „Isolation of the human ml (Hml) muscarinic acetylcholine receptor gene by PCR amplification.”. Nucleic Acids Res. 18 (8): 2191. PMC 330717 . PMID 2336407. doi:10.1093/nar/18.8.2191.
Ashkenazi A, Ramachandran J, Capon DJ (1989). „Acetylcholine analogue stimulates DNA synthesis in brain-derived cells via specific muscarinic receptor subtypes.”. Nature. 340 (6229): 146—50. PMID 2739737. doi:10.1038/340146a0.
Bonner TI, Buckley NJ, Young AC, Brann MR (1987). „Identification of a family of muscarinic acetylcholine receptor genes.”. Science. 237 (4814): 527—32. PMID 3037705. doi:10.1126/science.3037705.
Peralta EG; Ashkenazi A; Winslow JW; et al. (1988). „Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors.”. EMBO J. 6 (13): 3923—9. PMC 553870 . PMID 3443095.
Allard WJ, Sigal IS, Dixon RA (1988). „Sequence of the gene encoding the human M1 muscarinic acetylcholine receptor.”. Nucleic Acids Res. 15 (24): 10604. PMC 339984 . PMID 3697105. doi:10.1093/nar/15.24.10604.
Svoboda P, Milligan G (1994). „Agonist-induced transfer of the alpha subunits of the guanine-nucleotide-binding regulatory proteins Gq and G11 and of muscarinic m1 acetylcholine receptors from plasma membranes to a light-vesicular membrane fraction.”. Eur. J. Biochem. 224 (2): 455—62. PMID 7925360. doi:10.1111/j.1432-1033.1994.00455.x.
Crespo P; Xu N; Daniotti JL; et al. (1994). „Signaling through transforming G protein-coupled receptors in NIH 3T3 cells involves c-Raf activation. Evidence for a protein kinase C-independent pathway.”. J. Biol. Chem. 269 (33): 21103—9. PMID 8063729.
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Mullaney I; Mitchell FM; McCallum JF; et al. (1993). „The human muscarinic M1 acetylcholine receptor, when express in CHO cells, activates and downregulates both Gq alpha and G11 alpha equally and non-selectively.”. FEBS Lett. 324 (2): 241—5. PMID 8508928. doi:10.1016/0014-5793(93)81401-K.
Courseaux A; Grosgeorge J; Gaudray P; et al. (1997). „Definition of the minimal MEN1 candidate area based on a 5-Mb integrated map of proximal 11q13. The European Consortium on Men1, (GENEM 1; Groupe d'Etude des Néoplasies Endocriniennes Multiples de type 1).”. Genomics. 37 (3): 354—65. PMID 8938448.
Ishiyama A, López I, Wackym PA (1998). „Molecular characterization of muscarinic receptors in the human vestibular periphery. Implications for pharmacotherapy.”. The American journal of otology. 18 (5): 648—54. PMID 9303164.
Ishizaka N; Noda M; Yokoyama S; et al. (1998). „Muscarinic acetylcholine receptor subtypes in the human iris.”. Brain Res. 787 (2): 344—7. PMID 9518684. doi:10.1016/S0006-8993(97)01554-0.
„Acetylcholine receptors (muscarinic): M₁”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Архивирано из оригинала 02. 01. 2015. г.

[Messer_2000-1] Messer, Jr, WS (20. 1. 2000). „Acetylcholine”. University of Toledo. Архивирано из оригинала 14. 10. 2007. г. Приступљено 27. 10. 2007.

[isbn1-55009-109-3-2] Johnson, Gordon (2002). PDQ Pharmacology (2nd изд.). Hamilton, Ontario: BC Decker Inc. стр. 311 pages. ISBN 1-55009-109-3.

[Richelson_2000-3] Richelson, Elliott (2000). „Cholinergic Transduction, Psychopharmacology - The Fourth Generation of Progress”. American College of Neuropsychopharmacology. Приступљено 27. 10. 2007.

[pmid8645172-4] Burford NT, Nahorski SR (1996). „Muscarinic m1 receptor-stimulated adenylate cyclase activity in Chinese hamster ovary cells is mediated by Gs alpha and is not a consequence of phosphoinositidase C activation”. Biochem. J. 315 (Pt 3): 883—8. PMC 1217289 . PMID 8645172.

[entrez-5] а ^б ^в ^г „Entrez Gene: CHRM1 cholinergic receptor, muscarinic 1”.

[Rang-6] а ^б ^в ^г ^д ^ђ ^е ^ж ^з ^и Rang HP, Dale MM, Ritter JM, Moore PK (2003). „10”. Pharmacology (5th изд.). Elsevier Churchill Livingstone. стр. 139. ISBN 0-443-07145-4.

[7] Uchimura N, North RA (1. 3. 1990). „Muscarine reduces inwardly rectifying potassium conductance in rat nucleus accumbens neurones”. J. Physiol. (Lond.). 422 (1): 369—80. PMC 1190137 . PMID 1693682.

[pmid19906975-8] Shirey JK, Brady AE, Jones PJ, Davis AA, Bridges TM, Kennedy JP, Jadhav SB, Menon UN, Xiang Z, Watson ML, Christian EP, Doherty JJ, Quirk MC, Snyder DH, Lah JJ, Levey AI, Nicolle MM, Lindsley CW, Conn PJ (2009). „A selective allosteric potentiator of the M1 muscarinic acetylcholine receptor increases activity of medial prefrontal cortical neurons and restores impairments in reversal learning”. J. Neurosci. 29 (45): 14271—86. PMC 2811323 . PMID 19906975. doi:10.1523/JNEUROSCI.3930-09.2009.

[pmid19047481-9] а ^б Marlo JE; Niswender CM; Days EL; et al. (2008). „Discovery and characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity”. Mol. Pharmacol. 75 (3): 577—88. PMC 2684909 . PMID 19047481. doi:10.1124/mol.108.052886.

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Muskarinski acetilholinski receptor M1