5-HT_2C receptor

5-hidroksitriptaminski (serotoninski) receptor 2C
5-hidroksitriptaminski (serotoninski) receptor 2C
Identifikatori
Simboli	HTR2C; 5-HT2C; 5-HTR2C; HTR1C
Vanjski ID	OMIM: 312861 MGI: 96281 HomoloGene: 20242 GeneCards: HTR2C Gene
Ontologija gena
Molekularna funkcija	• aktivnost fosfatidilinozitol fosfolipaze C; • receptorska aktivnost; • aktivnost G-protein spregnutog receptora; • aktivnost serotoninskog receptora; • proteinsko vezivanje; • vezivanje leka; • serotoninsko vezivanje; • vezivanje 1-(4-jodo-2,5-dimetoksifenil)propan-2-amina;
Celularna komponenta	• nukleus; • citoplazma; • ćelijska membrana; • integralno sa membranom;
Biološki proces	• cGMP biosintetički proces; • fosfatidilinozitolni biosintetički proces; • signalni put serotoninskog receptora; • sinaptička transmisija; • način ishrane; • respons na lek; • otpuštanje sekvestiranih jona kalcijuma citozol; • ERK1 i ERK2 kaskada;
Pregled RNK izražavanja
	podaci
Ortolozi
Vrsta	Čovek
Entrez	3358
Ensembl	ENSG00000147246
UniProt	P28335
RefSeq (mRNA)	NM_000868.2
RefSeq (protein)	NP_000859.1
Lokacija (UCSC)	Chr X:; 113.82 - 114.14 Mb
PubMed pretraga	[1]

5-HT_2C receptor je tip 5-HT receptor koji vezuje endogeni neurotransmiter serotonin (5-hidroksitriptamin, 5-HT). On je G protein-spregnuti receptor (GPCR) koji deluje kro G_q/G₁₁ i posreduje ekscitatornu neurotransmisiju. HTR2C isto tako označava humani gen koji kodira receptor,^[1]^[2] koji je lociran na X hromozomu. Pošto muškarci imaju jednu kopiju ovog gena, a kod žena jedna od kopija je represivna, polimorfizmi ovog receptora mogu da imaju različiti uticaj u zavisnosti od pola.

Distribucija

5-HT_2C receptori su distribuirani širom perifernog humanog mozga.

Funkcija

5-HT_2C receptor je jedno od mnogih mesta vezivanja serotonina. Aktivacija ovog receptora serotoninom inhibira otpuštanje dopamina i norepinefrina u pojedinim oblastima mozga.^[3]

5-HT_2C receptori imaju znatan udeo u regulaciji raspoloženja, anksioznosti, ishrani, i reproduktivnom ponašanju.^[4] 5-HT_2C receptori regulišu dopaminsko otpuštanje u striatumu, prefrontalnom korteksu, nucleus accumbensu, hipokampusu, hipotalamusu, i amigdali, između ostalih.

Ligandi

Agonisti

A-372,159
AL-38022A
Aripiprazol
CP-809,101
Fenfluramin
Lisurid
Lorkaserin
Mesulergin
MK-212
Naftilizopropilamin
Norfenfluramin
Org 12,962
Org 37,684
Oksaflozan
PNU-22394
Psihodelici
- Lisergamidi (LSD)
- Fenetilamini (2C-B, DOI, DOM, Meskalin)
- Piperazini (mCPP, TFMPP)
- Triptamini (5-MeO-DMT, Bufotenin, DMT, Psilocin)
Ro60-0175
Vabicaserin
WAY-629
WAY-161,503
YM-348

Antagonisti

Inverzni Agonisti

Antidepresivi
- Triciklični (Amitriptilin, Klomipramin, Imipramin, Nortriptilin)
- Tetraciklični (Mirtazapin, Mijanserin, Amoksapin)
Antihistamini (Cyproheptadine, Hydroxyzine, Latrepirdin)
Antipsihotici
- Tipični (Hlorpromazin, Flufenazin, Loksapin, Tioridazin)
- Atipični (Klozapin, Olanzapin, Kvetijapin, Risperidon, Ziprasidon)
Cinanserin
Deramciklan
Ketanserin
LY-53,857
Metergolin
Metiotepin
Pizotifen
Ritanserin
SB-206,553
SB-228,357
SB-243,213
SB-242,084

Interakcije

Za 5-HT_2C receptor je pokazano da interaguje sa MPDZ.^[5]^[6]

Vidi još

Reference

^ „Entrez Gene: HTR2C 5-hydroxytryptamine (serotonin) receptor 2C”.
^ Stam NJ, Vanderheyden P, van Alebeek C, Klomp J, de Boer T, van Delft AM, Olijve W (1994). „Genomic organisation and functional expression of the gene encoding the human serotonin 5-HT_2C receptor”. Eur. J. Pharmacol. 269 (3): 339—48. PMID 7895773. doi:10.1016/0922-4106(94)90042-6.
^ Alex KD, Yavanian GJ, McFarlane HG, Pluto CP, Pehek EA (2005). „Modulation of dopamine release by striatal 5-HT2C receptors”. Synapse. 55 (4): 242—51. PMID 15668911. doi:10.1002/syn.20109.
^ Heisler LK, Zhou L, Bajwa P, Hsu J, Tecott LH (2007). „Serotonin 5-HT_2C receptors regulate anxiety-like behavior”. Genes, Brain and Behavior. 6 (5): 491—6. PMID 17451451. doi:10.1111/j.1601-183X.2007.00316.x.
^ Becamel C, Figge A, Poliak S, Dumuis A, Peles E, Bockaert J, Lubbert H, Ullmer C (2001). „Interaction of serotonin 5-hydroxytryptamine type 2C receptors with PDZ10 of the multi-PDZ domain protein MUPP1”. J. Biol. Chem. United States. 276 (16): 12974—82. ISSN 0021-9258. PMID 11150294. doi:10.1074/jbc.M008089200.
^ Ullmer C, Schmuck K, Figge A, Lübbert H (1998). „Cloning and characterization of MUPP1, a novel PDZ domain protein”. FEBS Lett. NETHERLANDS. 424 (1-2): 63—8. ISSN 0014-5793. PMID 9537516. doi:10.1016/S0014-5793(98)00141-0.

Literatura

Niswender CM, Sanders-Bush E, Emeson RB (1999). „Identification and characterization of RNA editing events within the 5-HT2C receptor.”. Ann. N. Y. Acad. Sci. 861 (1 ADVANCES IN S): 38—48. PMID 9928237. doi:10.1111/j.1749-6632.1998.tb10171.x.
Hoyer D, Hannon JP, Martin GR (2002). „Molecular, pharmacological and functional diversity of 5-HT receptors.”. Pharmacol. Biochem. Behav. 71 (4): 533—54. PMID 11888546. doi:10.1016/S0091-3057(01)00746-8.
Raymond JR; Mukhin YV; Gelasco A; et al. (2002). „Multiplicity of mechanisms of serotonin receptor signal transduction.”. Pharmacol. Ther. 92 (2-3): 179—212. PMID 11916537. doi:10.1016/S0163-7258(01)00169-3.
Van Oekelen D, Luyten WH, Leysen JE (2003). „5-HT2A and 5-HT2C receptors and their atypical regulation properties.”. Life Sci. 72 (22): 2429—49. PMID 12650852. doi:10.1016/S0024-3205(03)00141-3.
Reynolds GP, Templeman LA, Zhang ZJ (2005). „The role of 5-HT2C receptor polymorphisms in the pharmacogenetics of antipsychotic drug treatment.”. Prog. Neuropsychopharmacol. Biol. Psychiatry. 29 (6): 1021—8. PMID 15953671. doi:10.1016/j.pnpbp.2005.03.019.
Millan MJ (2006). „Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies.”. Therapie. 60 (5): 441—60. PMID 16433010. doi:10.2515/therapie:2005065.
Milatovich A; Hsieh CL; Bonaminio G; et al. (1993). „Serotonin receptor 1c gene assigned to X chromosome in human (band q24) and mouse (bands D-F4).”. Hum. Mol. Genet. 1 (9): 681—4. PMID 1302605. doi:10.1093/hmg/1.9.681.
Saltzman AG; Morse B; Whitman MM; et al. (1992). „Cloning of the human serotonin 5-HT2 and 5-HT1C receptor subtypes.”. Biochem. Biophys. Res. Commun. 181 (3): 1469—78. PMID 1722404. doi:10.1016/0006-291X(91)92105-S.
Lappalainen J; Zhang L; Dean M; et al. (1995). „Identification, expression, and pharmacology of a Cys23-Ser23 substitution in the human 5-HT2c receptor gene (HTR2C).”. Genomics. 27 (2): 274—9. PMID 7557992. doi:10.1006/geno.1995.1042.
Tecott LH; Sun LM; Akana SF; et al. (1995). „Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors.”. Nature. 374 (6522): 542—6. PMID 7700379. doi:10.1038/374542a0.
Stam NJ; Vanderheyden P; van Alebeek C; et al. (1995). „Genomic organisation and functional expression of the gene encoding the human serotonin 5-HT2C receptor.”. Eur. J. Pharmacol. 269 (3): 339—48. PMID 7895773. doi:10.1016/0922-4106(94)90042-6.
Xie E, Zhu L, Zhao L, Chang LS (1996). „The human serotonin 5-HT2C receptor: complete cDNA, genomic structure, and alternatively spliced variant.”. Genomics. 35 (3): 551—61. PMID 8812491. doi:10.1006/geno.1996.0397.
Burns CM; Chu H; Rueter SM; et al. (1997). „Regulation of serotonin-2C receptor G-protein coupling by RNA editing.”. Nature. 387 (6630): 303—8. PMID 9153397. doi:10.1038/387303a0.
Brennan TJ; Seeley WW; Kilgard M; et al. (1997). „Sound-induced seizures in serotonin 5-HT2c receptor mutant mice.”. Nat. Genet. 16 (4): 387—90. PMID 9241279. doi:10.1038/ng0897-387.
Ullmer C, Schmuck K, Figge A, Lübbert H (1998). „Cloning and characterization of MUPP1, a novel PDZ domain protein.”. FEBS Lett. 424 (1-2): 63—8. PMID 9537516. doi:10.1016/S0014-5793(98)00141-0.
Samochowiec J; Smolka M; Winterer G; et al. (1999). „Association analysis between a Cys23Ser substitution polymorphism of the human 5-HT2c receptor gene and neuronal hyperexcitability.”. Am. J. Med. Genet. 88 (2): 126—30. PMID 10206230. doi:10.1002/(SICI)1096-8628(19990416)88:2<126::AID-AJMG6>3.0.CO;2-M.
Cargill M; Altshuler D; Ireland J; et al. (1999). „Characterization of single-nucleotide polymorphisms in coding regions of human genes.”. Nat. Genet. 22 (3): 231—8. PMID 10391209. doi:10.1038/10290.
Marshall SE, Bird TG, Hart K, Welsh KI (2000). „Unified approach to the analysis of genetic variation in serotonergic pathways.”. Am. J. Med. Genet. 88 (6): 621—7. PMID 10581480. doi:10.1002/(SICI)1096-8628(19991215)88:6<621::AID-AJMG9>3.0.CO;2-H.
Backstrom JR, Price RD, Reasoner DT, Sanders-Bush E (2000). „Deletion of the serotonin 5-HT_2C receptor PDZ recognition motif prevents receptor phosphorylation and delays resensitization of receptor responses.”. J. Biol. Chem. 275 (31): 23620—6. PMID 10816555. doi:10.1074/jbc.M000922200.

[entrez-1] „Entrez Gene: HTR2C 5-hydroxytryptamine (serotonin) receptor 2C”.

[pmid7895773-2] Stam NJ, Vanderheyden P, van Alebeek C, Klomp J, de Boer T, van Delft AM, Olijve W (1994). „Genomic organisation and functional expression of the gene encoding the human serotonin 5-HT_2C receptor”. Eur. J. Pharmacol. 269 (3): 339—48. PMID 7895773. doi:10.1016/0922-4106(94)90042-6.

[pmid15668911-3] Alex KD, Yavanian GJ, McFarlane HG, Pluto CP, Pehek EA (2005). „Modulation of dopamine release by striatal 5-HT2C receptors”. Synapse. 55 (4): 242—51. PMID 15668911. doi:10.1002/syn.20109.

[pmid17451451-4] Heisler LK, Zhou L, Bajwa P, Hsu J, Tecott LH (2007). „Serotonin 5-HT_2C receptors regulate anxiety-like behavior”. Genes, Brain and Behavior. 6 (5): 491—6. PMID 17451451. doi:10.1111/j.1601-183X.2007.00316.x.

[pmid11150294-5] Becamel C, Figge A, Poliak S, Dumuis A, Peles E, Bockaert J, Lubbert H, Ullmer C (2001). „Interaction of serotonin 5-hydroxytryptamine type 2C receptors with PDZ10 of the multi-PDZ domain protein MUPP1”. J. Biol. Chem. United States. 276 (16): 12974—82. ISSN 0021-9258. PMID 11150294. doi:10.1074/jbc.M008089200.

[pmid9537516-6] Ullmer C, Schmuck K, Figge A, Lübbert H (1998). „Cloning and characterization of MUPP1, a novel PDZ domain protein”. FEBS Lett. NETHERLANDS. 424 (1-2): 63—8. ISSN 0014-5793. PMID 9537516. doi:10.1016/S0014-5793(98)00141-0.

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