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Trace amine-associated receptor

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"TAAR" redirects here. For the musical instrument, see Taar.

Trace amine-associated receptors (TAARs), sometimes referred to as trace amine receptors (TAs or TARs), are a class of G protein-coupled receptors that were discovered in 2001.[1][2][3] TAAR1, the first of six functional human TAARs, has gained considerable interest in academic and proprietary pharmaceutical research due to its unique role as the endogenous receptor for trace amines – which are non-classical metabolic derivatives of phenylalanine and tryptophan – and related psychostimulants, particularly amphetamine and methamphetamine.[4][5][6][7][8][9] In 2004 it was shown that in mammals TAAR1 is also a receptor for thyronamines, decarboxylated and deiodinated metabolites of the thyroid hormones.[6] Based upon evidence in mammals, it has been proposed that TAAR2–TAAR9 may have a function as olfactory receptors for volatile amines.[10][11]

Animal TAAR complement

The following is a list of the TAARs contained in selected animal genomes:[1][12]

Receptor function and ligands

Human TAARs and their ligands
Group Naming
convention 		Prior names Known or putative function in humans[14] Known ligands References
Group 1 TAAR1 TA1  • Neuromodulation of biogenic amines in the CNS
 • Chemotaxis of leukocytes
 • Chemoreceptor for volatile odorants†		  • Trace amines (e.g., phenethylamine, N-methylphenethylamine)
 • Classical monoamines (e.g., dopamine, serotonin, histamine)
 • Substituted amphetamines (e.g., amphetamine)
 [4][15][16]
Group 1 TAAR2‡ GPR58  • Chemotaxis of leukocytes
 • Chemoreceptor for volatile odorants		 phenethylamine, tyramine, 3-iodothyronamine [15][16]
Group 1 TAAR3 GPR57, GPR57P Probably a pseudogene [13][15]
Group 1 TAAR4 – Not present in humans [15][17]
Group 2 TAAR5 PNR Chemoreceptor for volatile and foul odorants trimethylamine, N,N-dimethylethylamine (agonists)
3-iodothyronamine (inverse agonist)		 [15][17][18][19][20]
Group 3 TAAR6 – Chemoreceptor for volatile odorants [15][17]
Group 3 TAAR7 – Not present in humans [15][17]
Group 3 TAAR8 TA5, TRAR5,
TAR5, GPR102		 Chemoreceptor for volatile odorants
(Note: only known Gi/o-coupled TAAR)		 [15][17][21]
Group 3 TAAR9‡ TA3, TRAR3,
TAR3		 Chemoreceptor for volatile odorants [15][17]
†TAAR1 is not expressed in the human olfactory epithelium, but certain volatile odorants have been identified as agonists of hTAAR1;[22] hence, it's not an olfactory receptor in spite of its capacity for odorant detection.[22]
‡TAAR2 is inactive in a subset of the human population, as there is a polymorphism with a premature stop codon in 10–15% of Asians.[13]
‡TAAR9 is a functional receptor in most of the population, but has a polymorphism with a premature stop codon in 10–30%, depending on the population subgroup.[13]

See also

  • "Trace Amine Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.

References

  1. ^ a b Hussain A, Saraiva LR, Korsching SI (2009). "Positive Darwinian selection and the birth of an olfactory receptor clade in teleosts". PNAS. 106 (11): 4313–8. doi:10.1073/pnas.0803229106. PMC 2657432. PMID 19237578.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, Durkin MM, Lakhlani PP, Bonini JA, Pathirana S, Boyle N, Pu X, Kouranova E, Lichtblau H, Ochoa FY, Branchek TA, Gerald C (2001). "Trace amines: identification of a family of mammalian G protein-coupled receptors". PNAS. 98 (16): 8966–71. doi:10.1073/pnas.151105198. PMC 55357. PMID 11459929.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, Darland T, Suchland KL, Pasumamula S, Kennedy JL, Olson SB, Magenis RE, Amara SG, Grandy DK (2001). "Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor". Mol. Pharmacol. 60 (6): 1181–8. doi:10.1124/mol.60.6.1181. PMID 11723224.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ a b Miller GM (January 2011). "The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity". J. Neurochem. 116 (2): 164–176. doi:10.1111/j.1471-4159.2010.07109.x. PMC 3005101. PMID 21073468.
  5. ^ Lam VM, Espinoza S, Gerasimov AS, Gainetdinov RR, Salahpour A (June 2015). "In-vivo pharmacology of Trace-Amine Associated Receptor 1". Eur. J. Pharmacol. 763: 136–42. doi:10.1016/j.ejphar.2015.06.026. PMID 26093041.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ a b Scanlan TS, Suchland KL, Hart ME, Chiellini G, Huang Y, Kruzich PJ, Frascarelli S, Crossley DA, Bunzow JR, Ronca-Testoni S, Lin ET, Hatton D, Zucchi R, Grandy DK (2004). "3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone". Nat. Med. 10 (6): 638–42. doi:10.1038/nm1051. PMID 15146179.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ Lindemann L, Hoener MC (2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends Pharmacol. Sci. 26 (5): 274–81. doi:10.1016/j.tips.2005.03.007. PMID 15860375.
  8. ^ Hart ME, Suchland KL, Miyakawa M, Bunzow JR, Grandy DK, Scanlan TS (2006). "Trace amine-associated receptor agonists: synthesis and evaluation of thyronamines and related analogues". J. Med. Chem. 49 (3): 1101–12. doi:10.1021/jm0505718. PMID 16451074.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ Grandy DK (2007). "Trace amine-associated receptor 1-Family archetype or iconoclast?". Pharmacol. Ther. 116 (3): 355–390. doi:10.1016/j.pharmthera.2007.06.007. PMC 2767338. PMID 17888514.
  10. ^ Liberles SD, Buck LB (2006). "A second class of chemosensory receptors in the olfactory epithelium". Nature. 442 (7103): 645–50. doi:10.1038/nature05066. PMID 16878137.
  11. ^ Liberles SD (July 2009). "Trace amine-associated receptors are olfactory receptors in vertebrates". Annals of the New York Academy of Sciences. 1170: 168–72. doi:10.1111/j.1749-6632.2009.04014.x. PMID 19686131.
  12. ^ Maguire JJ, Parker WA, Foord SM, Bonner TI, Neubig RR, Davenport AP (March 2009). "International Union of Pharmacology. LXXII. Recommendations for trace amine receptor nomenclature". Pharmacol. Rev. 61 (1): 1–8. doi:10.1124/pr.109.001107. PMC 2830119. PMID 19325074.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  13. ^ a b c d Davenport AP, Alexander SP, Sharman JL, Pawson AJ, Benson HE, Monaghan AE, Liew WC, Mpamhanga CP, Bonner TI, Neubig RR, Pin JP, Spedding M, Harmar AJ (July 2013). "International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list: recommendations for new pairings with cognate ligands". Pharmacol. Rev. 65 (3): 967–86. doi:10.1124/pr.112.007179. PMC 3698937. PMID 23686350. TAAR2 and TAAR9 Two of the trace amine receptors are inactivated in a portion of the human population. There is a polymorphism in TAAR2 (rs8192646) producing a premature stop codon at amino acid 168 in 10–15% of Asians. TAAR9 (formerly TRAR3) appears to be functional in most individuals but has a polymorphic premature stop codon at amino acid 61 (rs2842899) with an allele frequency of 10–30% in different populations (Vanti et al., 2003). TAAR3 (formerly GPR57) and TAAR4 (current gene symbol, TAAR4P) are thought to be pseudogenes in man though functional in rodents (Lindemann et al., 2005).{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ^ Liberles SD, Buck LB (2006). "A second class of chemosensory receptors in the olfactory epithelium". Nature. 442 (7103): 645–50. doi:10.1038/nature05066. PMID 16878137.
  15. ^ a b c d e f g h i "Trace amine receptor: Introduction". International Union of Basic and Clinical Pharmacology. Retrieved 15 February 2014.
  16. ^ a b Babusyte A, Kotthoff M, Fiedler J, Krautwurst D (March 2013). "Biogenic amines activate blood leukocytes via trace amine-associated receptors TAAR1 and TAAR2". J. Leukoc. Biol. 93 (3): 387–94. doi:10.1189/jlb.0912433. PMID 23315425.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. ^ a b c d e f Offermanns, Stefan (2008). Encyclopedia of Molecular Pharmacology (2nd ed.). Berlin: Springer. pp. 1219–1222. ISBN 3540389164. {{cite book}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  18. ^ Wallrabenstein I, Kuklan J, Weber L, Zborala S, Werner M, Altmüller J, Becker C, Schmidt A, Hatt H, Hummel T, Gisselmann G (2013). "Human trace amine-associated receptor TAAR5 can be activated by trimethylamine". PLoS ONE. 8 (2): e54950. doi:10.1371/journal.pone.0054950. PMC 3564852. PMID 23393561.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  19. ^ Zhang J, Pacifico R, Cawley D, Feinstein P, Bozza T (February 2013). "Ultrasensitive detection of amines by a trace amine-associated receptor". J. Neurosci. 33 (7): 3228–39. doi:10.1523/JNEUROSCI.4299-12.2013. PMC 3711460. PMID 23407976. We show that hT5 responds to the tertiary amine N,N-dimethylethylamine and to a lesser extent to trimethylamine, a structurally related agonist for mouse and rat TAAR5 (Liberles and Buck, 2006; Staubert et al., 2010; Ferrero et al., 2012).{{cite journal}}: CS1 maint: multiple names: authors list (link)
  20. ^ Dinter J, Mühlhaus J, Wienchol CL, Yi CX, Nürnberg D, Morin S, Grüters A, Köhrle J, Schöneberg T, Tschöp M, Krude H, Kleinau G, Biebermann H (2015). "Inverse agonistic action of 3-iodothyronamine at the human trace amine-associated receptor 5". PLoS ONE. 10 (2): e0117774. doi:10.1371/journal.pone.0117774. PMID 25706283.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  21. ^ Mühlhaus J, Dinter J, Nürnberg D, Rehders M, Depke M, Golchert J, Homuth G, Yi CX, Morin S, Köhrle J, Brix K, Tschöp M, Kleinau G, Biebermann H (2014). "Analysis of human TAAR8 and murine Taar8b mediated signaling pathways and expression profile". Int J Mol Sci. 15 (11): 20638–55. doi:10.3390/ijms151120638. PMC 4264187. PMID 25391046.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  22. ^ a b Zucchi R, Chiellini G, Scanlan TS, Grandy DK (December 2006). "Trace amine-associated receptors and their ligands". Br. J. Pharmacol. 149 (8): 967–78. doi:10.1038/sj.bjp.0706948. PMC 2014643. PMID 17088868.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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