Serotoniinireseptori
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
muokkaaTyyppi | 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
muokkaaPäätyypit jakautuvat edelleen alatyyppeihin, joilla on tiettyjä erityisominaisuuksia:[4][5][6]
Yleiskatsaus serotoniinireseptoreista | |||||
Reseptori | Geeni(t) | Sijaintipaikat | Tehtävä | Agonistit | Antagonistit |
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5-HT1A |
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5-HT1B |
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5-HT1D |
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5-HT1e otaksuttu olemassa olevaksi |
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5-HT1F |
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5-HT2A |
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5-HT2B |
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5-HT2C |
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5-HT3 |
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5-HT4 |
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5-HT5A |
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5-HT6 |
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5-HT7 |
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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
muokkaa- ↑ 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.
- ↑ 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
- ↑ 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
- ↑ Glennon RA, Dukat M, Westkaemper RB: Serotonin Receptor Subtypes and Ligands 1.1.2000. American College of Neurophyscopharmacology. Viitattu 11.4.2008.
- ↑ 5-Hydroxytryptamine Receptors IUPHAR Receptor Database. International Union of Basic and Clinical Pharmacology. Viitattu 11.4.2008.
- ↑ 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)
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
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- ↑ 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
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- ↑ 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
- ↑ Yasuno F, Suhara T, Nakayama T, Ichimiya T, Okubo Y, Takano A, Ando T, Inoue M, Maeda J, Suzuki K: Inhibitory effect of hippocampal 5-HT1A receptors on human explicit memory. Am J Psychiatry, 2003, 160. vsk, nro 2, s. 334–40. PubMed:12562581 doi:10.1176/appi.ajp.160.2.334
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- ↑ Bardin L, Tarayre JP, Malfetes N, Koek W, Colpaert FC.: Profound, non-opioid analgesia produced by the high-efficacy 5-HT(1A) agonist F 13640 in the formalin model of tonic nociceptive pain. Pharmacology., 2003, 67. vsk, nro 4, s. 182–194. PubMed:12595749 doi:10.1159/000068404
- ↑ 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
- ↑ Prow MR, Martin KF, Heal DJ: 8-OH-DPAT-induced mydriasis in mice: a pharmacological characterisation. Eur J Pharmacol., 1996, 317. vsk, nro 1, s. 21–8. PubMed:8982715 doi:10.1016/S0014-2999(96)00693-0
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- ↑ Monti JM, Jantos H: Dose-dependent effects of the 5-HT1A receptor agonist 8-OH-DPAT on sleep and wakefulness in the rat. J Sleep Res., 1992, 1. vsk, nro 3, s. 169–175. PubMed:10607047 doi:10.1111/j.1365-2869.1992.tb00033.x
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- ↑ Ootsuka Y, Blessing WW.: Activation of 5-HT1A receptors in rostral medullary raphé inhibits cutaneous vasoconstriction elicited by cold exposure in rabbits. Brain Res., 2006, 1073-1074. vsk, s. 252–61. PubMed:16455061 doi:10.1016/j.brainres.2005.12.031
- ↑ a b c d e f g h i j k l m n o p q r s t u v pharmamotion.com > Serotonin (5-HT): receptors, agonists and antagonists By Flavio Guzmán, M.D. on 9/08/09
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- ↑ Harrison AA, Parsons LH, Koob GF, Markou A: RU 24969, a 5-HT1A/1B agonist, elevates brain stimulation reward thresholds: an effect reversed by GR 127935, a 5-HT1B/1D antagonist. Psychopharmacology (Berl)., 1999, 141. vsk, nro 3, s. 242–50. PubMed:10027505 doi:10.1007/s002130050831
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