Wikipedia

Serotoniinireseptori

(Ohjattu sivulta 5-HT3-reseptori)

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]

Serotoniini.

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

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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

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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

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  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
  3. ↑ Francken BJ, Jurzak M, Vanhauwe JF, Luyten WH, Leysen JE.: The human 5-ht5A receptor couples to Gi/Go proteins and inhibits adenylate cyclase in HEK 293 cells. Eur J Pharmacol., 1998, 361. vsk, nro 2–3, s. 299–309. PubMed:9865521 doi:10.1016/S0014-2999(98)00744-4
  4. ↑ Glennon RA, Dukat M, Westkaemper RB: Serotonin Receptor Subtypes and Ligands 1.1.2000. American College of Neurophyscopharmacology. Viitattu 11.4.2008.
  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
  8. ↑ Müller CP, Carey RJ, Huston JP, De Souza Silva MA: Serotonin and psychostimulant addiction: focus on 5-HT1A-receptors. Prog Neurobiol., 2007, 81. vsk, nro 3, s. 133–78. PubMed:17316955 doi:10.1016/j.pneurobio.2007.01.001
  9. ↑ Carey RJ, DePalma G, Damianopoulos E, Shanahan A, Müller CP, Huston JP: Evidence that the 5-HT1A autoreceptor is an important pharmacological target for the modulation of cocaine behavioral stimulant effects. Brain Res., 2005, 1034. vsk, nro 1–2, s. 162–71. PubMed:15713268 doi:10.1016/j.brainres.2004.12.012
  10. ↑ a b de Boer SF, Koolhaas JM: 5-HT1A and 5-HT1B receptor agonists and aggression: a pharmacological challenge of the serotonin deficiency hypothesis. Eur J Pharmacol., 2005, 526. vsk, nro 1–3, s. 125–39. PubMed:16310183 doi:10.1016/j.ejphar.2005.09.065
  11. ↑ Parks CL, Robinson PS, Sibille E, Shenk T, Toth M: Increased anxiety of mice lacking the serotonin1A receptor. Proc Natl Acad Sci U S A., 1998, 195. vsk, nro 18, s. 10734–9. PubMed:9724773 PubMed Central:27964 doi:10.1073/pnas.95.18.10734
  12. ↑ Ebenezer IS, Arkle MJ, Tite RM: 8-Hydroxy-2-(di-n-propylamino)-tetralin inhibits food intake in fasted rats by an action at 5-HT1A receptors. Methods Find Exp Clin Pharmacol., 1998, 29. vsk, nro 4, s. 269–72. PubMed:17609739 doi:10.1358/mf.2007.29.4.1075362
  13. ↑ a b Wouters W, Tulp MT, Bevan P: Flesinoxan lowers blood pressure and heart rate in cats via 5-HT1A receptors. Eur J Pharmacol., 1998, 149. vsk, nro 3, s. 213–23. PubMed:2842163 doi:10.1016/0014-2999(88)90651-6
  14. ↑ a b Horiuchi J, McDowall LM, Dampney RA: Role of 5-HT(1A) receptors in the lower brainstem on the cardiovascular response to dorsomedial hypothalamus activation. Auton Neurosci., 2008, 142. vsk, nro 1–2, s. 71–6. PubMed:18667366 doi:10.1016/j.autneu.2008.06.004
  15. ↑ Nalivaiko E, Ootsuka Y, Blessing WW.: Activation of 5-HT1A receptors in the medullary raphe reduces cardiovascular changes elicited by acute psychological and inflammatory stresses in rabbits. Am J Physiol Regul Integr Comp Physiol., 2005, 289. vsk, nro 2, s. R596–R604. PubMed:15802554 doi:10.1152/ajpregu.00845.2004
  16. ↑ a b Lucot JB.: Antiemetic effects of flesinoxan in cats: comparisons with 8-hydroxy-2-(di-n-propylamino)tetralin. Eur J Pharmacol., 1994, 253. vsk, nro 1–2, s. 53–60. PubMed:8013549 doi:10.1016/0014-2999(94)90756-0
  17. ↑ Winstanley CA, Theobald DE, Dalley JW, Robbins TW.: Interactions between serotonin and dopamine in the control of impulsive choice in rats: therapeutic implications for impulse control disorders. Neuropsychopharmacology., 2005, 30. vsk, nro 4, s. 669–682. PubMed:15688093 doi:10.1038/sj.npp.1300610
  18. ↑ Ogren SO, Eriksson TM, Elvander-Tottie E, D'Addario C, Ekström JC, Svenningsson P, Meister B, Kehr J, Stiedl O: The role of 5-HT(1A) receptors in learning and memory. Behav Brain Res., 2008, 195. vsk, nro 1, s. 54–77. PubMed:18394726 doi:10.1016/j.bbr.2008.02.023
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  22. ↑ a b Millan MJ, Perrin-Monneyron S: Potentiation of fluoxetine-induced penile erections by combined blockade of 5-HT1A and 5-HT1B receptors. Eur J Pharmacol., 1997, 321. vsk, nro 3, s. 11–3. PubMed:9085055 doi:10.1016/S0014-2999(97)00050-2
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  31. ↑ a b c d Andrew D’Agostino, Clayton D. English, Jose A. Rey: Vortioxetine (Brintellix): A New Serotonergic Antidepressant. Pharmacy and Therapeutics, 2015-1, 40. vsk, nro 1, s. 36–40. PubMed:25628505 ISSN 1052-1372 Artikkelin verkkoversio.
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  61. ↑ a b Smriga M, Torii K: L-Lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in rats. Proc Natl Acad Sci U S A., 2003, 100. vsk, nro 26, s. 15370–5. PubMed:14676321 PubMed Central:307574 doi:10.1073/pnas.2436556100
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