5-HT1A receptor
| 5-hidroksitriptaminski (serotoninski) receptor 1A | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Identifikatori | |||||||||||
| Simboli | HTR1A; 5-HT1A; 5HT1a; ADRB2RL1; ADRBRL1 | ||||||||||
| Vanjski ID | OMIM: 109760 MGI: 96273 HomoloGene: 20148 IUPHAR: 5-HT1A GeneCards: HTR1A Gene | ||||||||||
| |||||||||||
| Pregled RNK izražavanja | |||||||||||
 | |||||||||||
| podaci | |||||||||||
| Ortolozi | |||||||||||
| Vrsta | Čovek | Miš | |||||||||
| Entrez | 3350 | 15550 | |||||||||
| Ensembl | ENSG00000178394 | ENSMUSG00000021721 | |||||||||
| UniProt | P08908 | Q8BGS4 | |||||||||
| RefSeq (mRNA) | NM_000524 | NM_008308 | |||||||||
| RefSeq (protein) | NP_000515 | NP_032334 | |||||||||
| Lokacija (UCSC) |
Chr 5: 63.29 - 63.29 Mb |
Chr 13: 106.56 - 106.57 Mb | |||||||||
| PubMed pretraga | [1] | [2] | |||||||||
5-HT1A receptor je tip 5-HT receptora za koji se vezuje endogeni neurotransmiter serotonin (5-hidroksitriptamin, 5-HT). On je G protein-spregnuti receptor (GPCR) koji je spregnut sa Gi/Go i posreduje inhibitornu neurotransmisiju. Akronim HTR1A označava humani gen koji kodira ovaj receptor.[1][2]
Distribucija
[uredi | uredi izvor]5-HT1A receptor najšire rasprostranjen od svih 5-HT receptora. U centralnom nervnom sistemu, 5-HT1A receptori se nalaze u cerebralnom kortesu, hipokampusu, septumu, amigdali, i rafovom jezgru u visokim koncentracijama, dok su u manjim količinama takođe prisutni u bazalnoj gangliji i talamusu.[3][4][5]
Funkcija
[uredi | uredi izvor]Neuromodulacija
[uredi | uredi izvor]5-HT1A receptorski agonisti snižavaju krvni pritisak i brzinu srca centralnim mehanizmom, indukcijom periferne vazodilaticije, i stimulacijom vagus nerva.[6] Ti efekti su rezultat aktivacije 5-HT1A receptora u rostralnoj ventrolateralnoj meduli.[6] Simpatolitički antihipertenzivni lek urapidil je antagonist α1-adrenergičkog receptora i agonist α2-adrenergičkog receptora, kao i agonist 5-HT1A receptora. Poznato je da ova zadnja osobina doprinosi njegovim sveukupnom terapeutskom dejstvu.[7][8] Vazodilatacija krvnih sudova kože centralnom 5-HT1A aktivacijom povećava toplotnu disipaciju sa organizma u okolnu sredinu, posledica čega je sniženje telesne temperature.[9][10]
Aktivacija centralnih 5-HT1A receptora inicira oslobađanje ili inhibiciju norepinefrina u zavisnosti od vrste, verovatno iz locus coeruleus regiona, što zatim dovodi do redukcije ili povišenja neuronskog tona sfinkter mišića zenice modulacijom postsinaptičkih α2-adrenergički receptora unutar Edinger-Vestfalnog jezgra, što dovodi do dilatacije zenica kod glodara, i kontrakcije zenica kod primata uključujući ljude.[11][12][13]
Agonisti 5-HT1A receptora kao što su buspiron[14] i flesinoksan[15] su delotvorni u olakšavanju anksioznosti[16] i depresije.[17] Buspiron i tandospiron su trenutno odobreni za te indikacije u mnogim zemljama. Drugi, poput gepirona,[18] flesinoksana,[19] flibanserina,[20] i PRX-00023[21] su takođe bili ispitivani, mada još uvek nisu potpuno razvijeni i odobreni. Neki od atipičnih antipsihotika kao što je aripiprazol[22] su takođe parcijalni agonisti 5-HT1A receptora i ponekad se koriste u niskim dozama kao zamena za standardne antidepresive kao što su selektivni inhibitori preuzimanja serotonina (SSRI).[23]
Endokrinologija
[uredi | uredi izvor]Aktivacija 5-HT1A receptora indukuje sekreciju raznih hormona među kojima su kortizol, kortikosteron, adrenokortikotropni hormon (ACTH), oksitocin, prolaktin, hormon rasta, i β-endorfin.[24][25][26][27] Ovaj receptor ne utiče na sekreciju vazopresina ili renina, za razliku od 5-HT2 receptora.[24][28] Postoje indikacije da otpuštanje oksitocina doprinosi prosocijalnim, antiagresivnim i anksiolitičkim svojstvima primećenim nakon aktivacije receptora.[28] Moguće je da sekrecija β-endorfina doprinosi antidepresivnim, anksiolitičkim, i analgetskim efektima.
Ligandi
[uredi | uredi izvor]Distribucija 5-HT1A receptora u ljudskom mozgu može biti snimljena pozitronskom emisionom tomografijom koristeći radioligand [11C]WAY-100,635.[29] Na primer, u jednoj studiji je utvrđeno povećano 5-HT1A vezivanje kod tipa 2 dijabetesa.[30] Jedna druga PET studija je utvrdila negativnu korelaciju između stepena 5-HT1A vezivanja u rafijevom jezgru, hipokampusu i neokorteksu, i samo-prijavljene tendencije doživljavanja duhovnih iskustava.[31] Kad je obeležen sa tricijumom, WAY-100,635 može takođe da se koristi u autoradiografiji.[32]
Agonisti
[uredi | uredi izvor]- 5-CT
- 5-MeO-DMT
- 5-MT
- 8-OH-DPAT
- Adatanserin
- αET
- Alnespiron
- αMT
- Aripiprazol
- Asenapin
- Bay R 1531
- Befiradol
- Binospiron
- Bufotenin
- Buspiron
- Kanabidiol
- Klozapin
- Dihidroergotamin
- DMT
- Ebalzotan
- Eltoprazin
- Eptapiron
- Ergotamin
- Etoperidon
- F-11,461
- F-12,826
- F-13,714
- F-14,679
- F-15,599
- Flesinoksan
- Flibanserin
- Gepiron
- Ipsapiron
- Lesopitron
- Lisurid
- LSD
- Lu AA21004
- LY-293,284
- LY-301,317
- MDMA
- MKC-242
- NBUMP
- Nefazodon
- Osemozotan
- Perospiron
- Piklozotan
- Psilocin
- Psilocibin
- PRX-00023
- Rauvolscin
- Repinotan
- RU-24,969
- S-15,535
- Sarizotan
- SSR-181,507
- Sunepitron
- Tandospiron
- Tiospiron
- Trazodon
- U-92,016-A
- Urapidil
- Vilazodon
- Johimbin
- Ksaliproden
- Zalospiron
- Ziprasidon
Antagonisti
[uredi | uredi izvor]Genetika
[uredi | uredi izvor]5-HT1A receptor je kodiran HTR1A genom. Postoji više humanih polimorfizama vezanih za ovaj gen. Jedan pregled iz 2007. navodi 27 jednonukleotidnih polimorfizama (SNP).[33] Najviše istraženi su C-1019G (rs6295), C-1018G,[34] Ile28Val (rs1799921), Arg219Leu (rs1800044), i Gly22Ser (rs1799920).[33] Neki od preostalih SNP-ova su Pro16Leu, Gly272Asp, i sinonimni polimorfizam G294A (rs6294). Varijante ovog gena su bile studirane u vezi sa psihijatrijskim poremećajima, ali definitivni rezultati nisu dobijeni.[33]
Interakcije
[uredi | uredi izvor]Za 5-HT1A receptor je pokazano da interaguje sa moždanim neurotrofnim faktorom (BDNF), koji učestvuje u regulaciji raspoloženja i anksioznosti.[35][36] Pokazano je da ostvaruje interakcije sa sfingozin-1-fosfatnim receptorom 1 (S1PR1).[37]
Vidi još
[uredi | uredi izvor]Reference
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Literatura
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