Encyclopedia of Signaling Molecules

Living Edition
| Editors: Sangdun Choi

Trace Amine-Associated Receptor 1 (TAAR1)

  • Vincent M. Lam
  • Raul R. Gainetdinov
  • Ali Salahpour
  • Stefano Espinoza
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-6438-9_101881-1

Synonyms

Historical Background

Trace amines (TAs) are a class of endogenous amines that traditionally include compounds such as β-phenylethylamine (b-PEA), tyramine, tryptamine, octopamine, and synephrine (Fig. 1) (Berry 2004). Trace amines are characterized by their trace levels in the brain, their lack of vesicular storage, and their fast metabolism. These molecules are structurally related to the classic monoamines (dopamine, norepinephrine, and serotonin) and share similar synthetic and degradation pathways. TAs are synthesized by the action of L-amino acid decarboxylase and are degraded primarily by monoamine oxidases (MAO-A and MAO-B) (Fig. 2). TAs were initially discovered over 100 years ago and are present in several organisms (Grandy 2007). In invertebrates, octopamine and tyramine serve as major neurotransmitters, functionally replacing the role of epinephrine and norepinephrine found in vertebrates. However, in vertebrates, in particular in mammals,...

Keywords

Prefrontal Cortex Ventral Tegmental Area Partial Agonist Dorsal Raphe NREM Sleep 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

References

  1. Babusyte A, Kotthoff M, Fiedler J, Krautwurst D. Biogenic amines activate blood leukocytes via trace amine-associated receptors TAAR1 and TAAR2. J Leukoc Biol. 2013;93:387–94. doi:10.1189/jlb.0912433. jlb.0912433. [pii].CrossRefPubMedGoogle Scholar
  2. Barak LS, Salahpour A, Zhang X, Masri B, Sotnikova TD, Ramsey AJ, et al. Pharmacological characterization of membrane-expressed human trace amine-associated receptor 1 (TAAR1) by a bioluminescence resonance energy transfer cAMP biosensor. Mol Pharmacol. 2008;74:585–94. doi:10.1124/mol.108.048884. mol.108.048884. [pii].CrossRefPubMedPubMedCentralGoogle Scholar
  3. Berry MD. Mammalian central nervous system trace amines. Pharmacologic amphetamines, physiologic neuromodulators. J Neurochem. 2004;90:257–71. doi:10.1111/j.1471-4159.2004.02501.x. JNC2501 [pii].CrossRefPubMedGoogle Scholar
  4. Black SW, Schwartz MD, Chen TM, Hoener MC, Kilduff TS. Trace amine-associated receptor 1 agonists as narcolepsy therapeutics. Biol Psychiatry. 2016. doi:10.1016/j.biopsych.2016.10.012.Google Scholar
  5. Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, et al. Trace amines: identification of a family of mammalian G protein-coupled receptors. Proc Natl Acad Sci USA. 2001;98:8966–71. doi:10.1073/pnas.151105198. 151105198 [pii].CrossRefPubMedPubMedCentralGoogle Scholar
  6. Bradaia A, Trube G, Stalder H, Norcross RD, Ozmen L, Wettstein JG, et al. The selective antagonist EPPTB reveals TAAR1-mediated regulatory mechanisms in dopaminergic neurons of the mesolimbic system. Proc Natl Acad Sci USA. 2009. doi:10.1073/pnas.0906522106. 0906522106 [pii].PubMedPubMedCentralGoogle Scholar
  7. Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, et al. Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor. Mol Pharmacol. 2001;60:1181–8.PubMedGoogle Scholar
  8. Cichero E, Espinoza S, Franchini S, Guariento S, Brasili L, Gainetdinov RR, et al. Further insights into the pharmacology of the human trace amine-associated receptors: discovery of novel ligands for TAAR1 by a virtual screening approach. Chem Biol Drug Des. 2014;84:712–20. doi:10.1111/cbdd.12367.CrossRefPubMedGoogle Scholar
  9. Espinoza S, Salahpour A, Masri B, Sotnikova TD, Messa M, Barak LS, et al. Functional interaction between trace amine-associated receptor 1 and dopamine D2 receptor. Mol Pharmacol. 2011;80:416–25. doi:10.1124/mol.111.073304.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Espinoza S, Ghisi V, Emanuele M, Leo D, Sukhanov I, Sotnikova TD, et al. Postsynaptic D2 dopamine receptor supersensitivity in the striatum of mice lacking TAAR1. Neuropharmacology. 2015a;93:308–13. doi:10.1016/j.neuropharm.2015.02.010.CrossRefPubMedGoogle Scholar
  11. Espinoza S, Lignani G, Caffino L, Maggi S, Sukhanov I, Leo D, et al. TAAR1 modulates cortical glutamate NMDA receptor function. Neuropsychopharmacology. 2015b;40:2217–27. doi:10.1038/npp.2015.65.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Ferragud A, Howell AD, Moore CF, Ta TL, Hoener MC, Sabino V, et al. The trace amine-associated receptor 1 agonist RO5256390 blocks compulsive, binge-like eating in rats. Neuropsychopharmacology. 2016. doi:10.1038/npp.2016.233.PubMedGoogle Scholar
  13. Grandy DK. Trace amine-associated receptor 1-family archetype or iconoclast? Pharmacol Ther. 2007;116:355–90. doi:10.1016/j.pharmthera.2007.06.007. S0163-7258(07)00145-3 [pii].CrossRefPubMedPubMedCentralGoogle Scholar
  14. Harkness JH, Shi X, Janowsky A, Phillips TJ. Trace amine-associated receptor 1 regulation of methamphetamine intake and related traits. Neuropsychopharmacology. 2015;40:2175–84. doi:10.1038/npp.2015.61.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Harmeier A, Obermueller S, Meyer CA, Revel FG, Buchy D, Chaboz S, et al. Trace amine-associated receptor 1 activation silences GSK3beta signaling of TAAR1 and D2R heteromers. Eur Neuropsychopharmacol. 2015. doi:10.1016/j.euroneuro.2015.08.011.PubMedGoogle Scholar
  16. Hu LA, Zhou T, Ahn J, Wang S, Zhou J, Hu Y, et al. Human and mouse trace amine-associated receptor 1 have distinct pharmacology towards endogenous monoamines and imidazoline receptor ligands. Biochem J. 2009;424:39–45. doi:10.1042/BJ20090998.CrossRefPubMedGoogle Scholar
  17. Lam VM, Rodríguez, Zhang T, Koh EJ, Carlsson J, Salahpour A. Discovery of tace amine-assoicated receptor 1 ligands by molecular docking screening against a homology model. Med Chem Comm. 2015;12:2216–2223. doi: 10.1039/C5MD00400DGoogle Scholar
  18. Leo D, Mus L, Espinoza S, Hoener MC, Sotnikova TD, Gainetdinov RR. Taar1-mediated modulation of presynaptic dopaminergic neurotransmission: role of D2 dopamine autoreceptors. Neuropharmacology. 2014;81:283–91. doi:10.1016/j.neuropharm.2014.02.007.CrossRefPubMedGoogle Scholar
  19. Lindemann L, Ebeling M, Kratochwil NA, Bunzow JR, Grandy DK, Hoener MC. Trace amine-associated receptors form structurally and functionally distinct subfamilies of novel G protein-coupled receptors. Genomics. 2005;85:372–85. doi:10.1016/j.ygeno.2004.11.010. S0888-7543(04)00316-7 [pii].CrossRefPubMedGoogle Scholar
  20. Lindemann L, Meyer CA, Jeanneau K, Bradaia A, Ozmen L, Bluethmann H, et al. Trace amine-associated receptor 1 modulates dopaminergic activity. J Pharmacol Exp Ther. 2008;324:948–56. doi:10.1124/jpet.107.132647. jpet.107.132647 [pii].CrossRefPubMedGoogle Scholar
  21. Liu JF, Siemian JN, Seaman Jr R, Zhang Y, Li JX. Role of TAAR1 within the subregions of the mesocorticolimbic dopaminergic system in cocaine-seeking behavior. J Neurosci. 2017;37:882–92. doi:10.1523/JNEUROSCI.2006-16.2017.CrossRefPubMedGoogle Scholar
  22. Pei Y, Lee JA, Leo D, Gainetdinov RR, Hoener MC, Canales JJ. Activation of the trace amine-associated receptor 1 prevents relapse to cocaine seeking. Neuropsychopharmacology. 2014. doi:10.1038/npp.2014.88. npp201488 [pii].PubMedPubMedCentralGoogle Scholar
  23. Raab S, Wang H, Uhles S, Cole N, Alvarez-Sanchez R, Kunnecke B, et al. Incretin-like effects of small molecule trace amine-associated receptor 1 agonists. Mol Metab. 2016;5:47–56. doi:10.1016/j.molmet.2015.09.015.CrossRefPubMedGoogle Scholar
  24. Revel FG, Moreau JL, Gainetdinov RR, Bradaia A, Sotnikova TD, Mory R, et al. TAAR1 activation modulates monoaminergic neurotransmission, preventing hyperdopaminergic and hypoglutamatergic activity. Proc Natl Acad Sci USA. 2011;108:8485–90. doi:10.1073/pnas.1103029108. 1103029108 [pii].CrossRefPubMedPubMedCentralGoogle Scholar
  25. Revel FG, Moreau JL, Gainetdinov RR, Ferragud A, Velazquez-Sanchez C, Sotnikova TD, et al. Trace amine-associated receptor 1 partial agonism reveals novel paradigm for neuropsychiatric therapeutics. Biol Psychiatry. 2012;72:934–42. doi:10.1016/j.biopsych.2012.05.014. S0006-3223(12)00459-3 [pii].CrossRefPubMedGoogle Scholar
  26. Revel FG, Moreau JL, Pouzet B, Mory R, Bradaia A, Buchy D, et al. A new perspective for schizophrenia: TAAR1 agonists reveal antipsychotic- and antidepressant-like activity, improve cognition and control body weight. Mol Psychiatry. 2013;18:543–56. doi:10.1038/mp.2012.57. mp201257 [pii].CrossRefPubMedGoogle Scholar
  27. Scanlan TS, Suchland KL, Hart ME, Chiellini G, Huang Y, Kruzich PJ, et al. 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone. Nat Med. 2004;10:638–42. doi:10.1038/nm1051. nm1051 [pii].CrossRefPubMedGoogle Scholar
  28. Schwartz MD, Black SW, Fisher SP, Palmerston JB, Morairty SR, Hoener MC, et al. Trace amine-associated receptor 1 regulates wakefulness and EEG spectral composition. Neuropsychopharmacology. 2016. doi:10.1038/npp.2016.216.Google Scholar
  29. Sotnikova TD, Beaulieu JM, Espinoza S, Masri B, Zhang X, Salahpour A, et al. The dopamine metabolite 3-methoxytyramine is a neuromodulator. PLoS One. 2010;5:e13452. doi:10.1371/journal.pone.0013452.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Thorn DA, Jing L, Qiu Y, Gancarz-Kausch AM, Galuska CM, Dietz DM, et al. Effects of the trace amine associated receptor 1 agonist RO5263397 on abuse-related effects of cocaine in rats. Neuropsychopharmacology. 2014. doi:10.1038/npp.2014.91. npp201491 [pii].PubMedPubMedCentralGoogle Scholar
  31. Wolinsky TD, Swanson CJ, Smith KE, Zhong H, Borowsky B, Seeman P, et al. The trace amine 1 receptor knockout mouse: an animal model with relevance to schizophrenia. Genes Brain Behav. 2007;6:628–39. doi:10.1111/j.1601-183X.2006.00292.x. GBB292 [pii].CrossRefPubMedGoogle Scholar
  32. Xie Z, Miller GM. Trace amine-associated receptor 1 is a modulator of the dopamine transporter. J Pharmacol Exp Ther. 2007;321:128–36. doi:10.1124/jpet.106.117382. jpet.106.117382 [pii].CrossRefPubMedGoogle Scholar
  33. Xie Z, Miller GM. Trace amine-associated receptor 1 as a monoaminergic modulator in brain. Biochem Pharmacol. 2009;78:1095–104. doi:10.1016/j.bcp.2009.05.031. S0006-2952(09)00440-7 [pii].CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  1. 1.Department of Pharmacology and ToxicologyUniversity of TorontoTorontoCanada
  2. 2.Institute of Translational BiomedicineSt. Petersburg State UniversitySt. PetersburgRussia
  3. 3.Skolkovo Institute of Science and Technology (Skoltech)MoscowRussia
  4. 4.Department of Neuroscience and Brain TechnologiesIstituto Italiano di TecnologiaGenoaItaly