Serotoniinireseptori

Serotoniini.

Serotoniinireseptori eli 5-HT-reseptori on monien eliölajien, muun muassa ihmisen reseptori, johon muun muassa välittäjäaine serotoniini voi kiinnittyä luonnollisena ligandina. Reseptoreita on seitsemää tyyppiä, 5-HT1–7, jotka jakautuvat edelleen lukuisiin alatyyppeihin. Niitä on sekä keskus- että ääreishermostossa. Osa reseptoreista toimii kiihdyttävinä ja osa vaimentavina eli hermosolun toimintaa estävinä.[1][2]

Serotoniinireseptorit moduloivat monien välittäjäaineiden vapautumista; tällaisia ovat esimerkiksi GABA, dopamiini, adrenaliini / noradrenaliini ja asetyylikoliini. Sama pätee moniin hormoneihin; näitä ovat muun muassa oksitosiini, prolaktiini, vasopressiini, kortisoli, kortikotropiini ja substanssi P. Serotoniinireseptorit vaikuttavat moniin biologisiin prosesseihin, kuten aggressioon, levottomuuteen, ruokahaluun, kognitioon, oppimiseen, muistiin, mielialaan, pahoinvointiin, uneen ja lämmönsäätelyyn. Ne ovat myös monien lääkkeiden ja päihteiden vaikutuskohteita; näitä ovat muun muassa monet antidepressantit, antipsykootit, laihdutusvalmisteet, antiemeetit, prokineetit, migreenilääkkeet, hallusinogeenit ja entaktogeenit.

Lukuun ottamatta 5-HT3-reseptoria, joka on ionikanavareseptori, kaikki muut serotoniinireseptorit ovat G-proteiinikytkentäisiä reseptoreja, jotka aktivoivat toisiolähettejä hermosolun sisällä, jotta viesti välittyy eteenpäin.

Tyypit

Tyyppi Toimintatyyppi Mekanismi Vaikutustapa
5-HT1 Gi/Go-proteiinikytkentäinen. Solun cAMP-tason vähentäminen. Estävä
5-HT2 Gq/G11-proteiinikytkentäinen. Solun IP3- ja DAG-tasojen lisääminen. Kiihdyttävä
5-HT3 Ligandiporttinen Na+ ja K+ -kationikanava. Plasmakalvon depolarisointi. Kiihdyttävä
5-HT4 Gs-proteiinikytkentäinen. Solun cAMP-tason lisääminen. Kiihdyttävä
5-HT5 Gi/Go-proteiinikytkentäinen.[3] Solun cAMP-tason vähentäminen. Estävä
5-HT6 Gs-proteiinikytkentäinen. Solun cAMP-tason lisääminen. Kiihdyttävä
5-HT7 Gs-proteiinikytkentäinen. Solun cAMP-tason lisääminen. Kiihdyttävä

Alatyypit

Päätyypit jakautuvat edelleen alatyyppeihin, joilla on tiettyjä erityisominaisuuksia:[4][5][6]

Yleiskatsaus serotoniinireseptoreista
Reseptori Geeni(t) Sijaintipaikat Tehtävä Agonistit Antagonistit
5-HT1A
  • Verisuonet
  • Keskushermosto
5-HT1B
  • Verisuonet
  • Keskushermosto
5-HT1D
  • Verisuonet
  • Keskushermosto
  • Hätääntyneisyys[38][39]
  • Liikkeet[37]
  • Verisuonten supistuminen
5-HT1e otaksuttu olemassa olevaksi
  • Verisuonet
  • Keskushermosto
5-HT1F
  • Keskushermosto
  • Migreeni
  • LY334370
  • COL-144
5-HT2A
  • Verisuonet
  • Keskushermosto
  • Ruoansulatuskanava
  • Verihiutaleet
  • Ääreishermosto
  • Sileä lihaskudos
  • Riippuvuus (mahdollisesti moduloiva) [40]
  • Hätääntyneisyys[41]
  • Ruokahalu
  • Kognitio
  • Mielikuvitus
  • Oppiminen
  • Muisti
  • Mieliala
  • Havaintokyky
  • Seksuaalinen käytös[42]
  • Uni[43]
  • Lämmönsäätely[44]
  • Verisuonten supistuminen[45]
5-HT2B
  • Verisuonet
  • Keskushermosto
  • Ruoansulatuskanava
  • Verihiutaleet
  • Ääreishermosto
  • Sileä lihaskudos
5-HT2C
  • Verisuonet
  • Keskushermosto
  • Ruoansulatuskanava
  • Verihiutaleet
  • Ääreishermosto
  • Sileä lihaskudos
  • Riippuvuus. (mahdollisesti moduloiva)[40]
  • Hätääntyneisyys[51][52][53]
  • Ruokahalu
  • Ruoansulatuskanavan liikkuvuus[54]
  • Liikkeet
  • Mieliala[52][53]
  • Siittimen erektio[55][56]
  • Seksuaalinen käytös[42]
  • Uni[57]
  • Lämmönsäätely[44]
  • Verisuonten supistuminen
5-HT3
  • Keskushermosto
  • Ruoansulatuskanava
  • Ääreishermosto
  • Riippuvuus
  • Hätääntyneisyys
  • Oksentaminen
  • Ruoansulatuskanavan liikkuvuuslähde?
  • Oppiminen[59]
  • Muisti[59]
  • Pahoinvointi
5-HT4
  • Keskushermosto
  • Ruoansulatuskanava
  • Ääreishermosto
5-HT5A
  • Keskushermosto
5-HT6
  • Keskushermosto
5-HT7
  • Verisuonet
  • Keskushermosto
  • Ruoansulatuskanava

5-HT1C -nimistä reseptoria ei ole, koska sellaiseksi alun perin nimetty serotoniinireseptori kloonattiin ja sitä tutkittiin tarkemmin, jolloin sillä havaittiin olevan enemmän yhteistä 5-HT2 -tyypin reseptorien kanssa ja sen uudeksi nimeksi vakiintui 5-HT2C. 5-HT5B-reseptori on ainoastaan hiirillä ja rotilla, eikä lainkaan ihmisillä tai apinoilla.

Erittäin epäselektiivisiä serotoniiniagonisteja ovat muun muassa ergotamiini (migreenilääke), joka aktivoi 5-HT1A-, 5-HT1D-, 5-HT1B-, D2- ja noradrenaliinireseptoreita.[30] LSD (psykedeeli) on 5-HT1A-, 5-HT2A-, 5-HT2C-, 5-HT5A-, 5-HT5- ja 5-HT6-reseptoreiden agonisti.[30]

Lähteet

  1. ↑ Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PP: International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). Pharmacol. Rev., 1994, 46. vsk, nro 2, s. 157–203. PubMed:7938165 Artikkelin verkkoversio.
  2. ↑ Frazer A, Hensler JG: ”Chapter 13: Serotonin Receptors”, Basic Neurochemistry: Molecular, Cellular, and Medical Aspects, s. 263–292. Philadelphia: Lippincott-Raven, 1999. ISBN 0-397-51820-X
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  5. ↑ 5-Hydroxytryptamine Receptors IUPHAR Receptor Database. International Union of Basic and Clinical Pharmacology. Viitattu 11.4.2008.
  6. ↑ Wesolowska A: In the search for selective ligands of 5-HT5, 5-HT6 and 5-HT7 serotonin receptors. Polish Journal of Pharmacology, 2002, 54. vsk, nro 4, s. 327–41. PubMed:12523486 Artikkelin verkkoversio. (PDF)
  7. ↑ Tomkins DM, Higgins GA, Sellers EM: Low doses of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH DPAT) increase ethanol intake. Psychopharmacology (Berl)., 1994, 115. vsk, nro 1–2, s. 173–9. PubMed:7862892 doi:10.1007/BF02244769
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