Six human trace amine-associated receptors (hTAARs) – hTAAR1, hTAAR2, hTAAR5, hTAAR6, hTAAR8, and hTAAR9 – have been identified and partially characterized. The table below contains summary information from literature reviews, pharmacology databases, and supplementary primary research articles on the expression profiles, signal transduction mechanisms, ligands, and physiological functions of these receptors.
The pharmacology and molecular biology of human trace amine-associated receptors
^As of December 2017,[update] the functions of hTAAR2, hTAAR5, hTAAR6, hTAAR8, and hTAAR9 in the CNS and peripheral tissues outside the olfactory epithelium have not been determined.[13]
^hTAAR1 is the only TAAR subtype that is not expressed within the human olfactory epithelium.[9][14] Hence, unlike all other human trace amine-associated receptors, hTAAR1 does not function as an olfactory receptor in humans.[9][14]
A review of studies involving non-human animals indicated that TAARs in the olfactory epithelium can mediate attractive or aversive behavioral responses to an agonist.[9] This review also noted that the behavioral response evoked by a TAAR can vary across species.[9] For example, TAAR5 mediates attraction to trimethylamine in mice and aversion to trimethylamine in rats.[9] In humans, hTAAR5 presumably mediates aversion to trimethylamine, which is known to act as an hTAAR5 agonist and to possess a foul, fishy odor that is aversive to humans;[9][19] however, hTAAR5 is not the only olfactory receptor that is responsible for trimethylamine olfaction in humans.[9][19] As of December 2015,[update] hTAAR5-mediated trimethylamine aversion has not been examined in published research.[19]
Ulotaront / SEP 363856 is a TAAR1 agonist in phase 3 clinical trials for schizophrenia and earlier trials for Parkinson's Disease psychosis. The medicine has obtained Breakthrough designation from the US FDA.[30][31][32]
This section needs expansion with: coverage of relevant material from this review[13]. You can help by adding to it. (March 2018)
^Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, et al. (July 2001). "Trace amines: identification of a family of mammalian G protein-coupled receptors". Proceedings of the National Academy of Sciences of the United States of America. 98 (16): 8966–8971. doi:10.1073/pnas.151105198. PMC55357. PMID 11459929.
^Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, et al. (December 2001). "Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor". Molecular Pharmacology. 60 (6): 1181–1188. doi:10.1124/mol.60.6.1181. PMID 11723224.
^ abMiller GM (January 2011). "The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity". Journal of Neurochemistry. 116 (2): 164–176. doi:10.1111/j.1471-4159.2010.07109.x. PMC3005101. PMID 21073468.
^Lam VM, Espinoza S, Gerasimov AS, Gainetdinov RR, Salahpour A (September 2015). "In-vivo pharmacology of Trace-Amine Associated Receptor 1". European Journal of Pharmacology. 763 (Pt B): 136–142. doi:10.1016/j.ejphar.2015.06.026. PMID 26093041.
^ abScanlan TS, Suchland KL, Hart ME, Chiellini G, Huang Y, Kruzich PJ, et al. (June 2004). "3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone". Nature Medicine. 10 (6): 638–642. doi:10.1038/nm1051. PMID 15146179. S2CID 2389946.
^Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends in Pharmacological Sciences. 26 (5): 274–281. doi:10.1016/j.tips.2005.03.007. PMID 15860375.
^Hart ME, Suchland KL, Miyakawa M, Bunzow JR, Grandy DK, Scanlan TS (February 2006). "Trace amine-associated receptor agonists: synthesis and evaluation of thyronamines and related analogues". Journal of Medicinal Chemistry. 49 (3): 1101–1112. doi:10.1021/jm0505718. PMID 16451074.
^ abcdefghijklmnopLiberles SD (October 2015). "Trace amine-associated receptors: ligands, neural circuits, and behaviors". Current Opinion in Neurobiology. 34: 1–7. doi:10.1016/j.conb.2015.01.001. PMC4508243. PMID 25616211. Roles for another receptor are supported by TAAR5-independent trimethylamine anosmias in humans [32]. ... Several TAARs detect volatile and aversive amines, but the olfactory system is capable of discarding ligand-based or function-based constraints on TAAR evolution. Particular TAARs have mutated to recognize new ligands, with almost an entire teleost clade losing the canonical amine-recognition motif. Furthermore, while some TAARs detect aversive odors, TAAR-mediated behaviors can vary across species. ... The ability of particular TAARs to mediate aversion and attraction behavior provides an exciting opportunity for mechanistic unraveling of odor valence encoding. Figure 2: Table of ligands, expression patterns, and species-specific behavioral responses for each TAAR
^Hussain A, Saraiva LR, Korsching SI (March 2009). "Positive Darwinian selection and the birth of an olfactory receptor clade in teleosts". Proceedings of the National Academy of Sciences of the United States of America. 106 (11): 4313–4318. Bibcode:2009PNAS..106.4313H. doi:10.1073/pnas.0803229106. PMC2657432. PMID 19237578.
^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". Pharmacological Reviews. 61 (1): 1–8. doi:10.1124/pr.109.001107. PMC2830119. PMID 19325074.
^ abcdeDavenport AP, Alexander SP, Sharman JL, Pawson AJ, Benson HE, Monaghan AE, et al. (July 2013). "International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list: recommendations for new pairings with cognate ligands". Pharmacological Reviews. 65 (3): 967–986. doi:10.1124/pr.112.007179. PMC3698937. 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).
^ abcdefghijklmnBerry MD, Gainetdinov RR, Hoener MC, Shahid M (December 2017). "Pharmacology of human trace amine-associated receptors: Therapeutic opportunities and challenges". Pharmacology & Therapeutics. 180: 161–180. doi:10.1016/j.pharmthera.2017.07.002. PMID 28723415.
^ abLiberles SD, Buck LB (August 2006). "A second class of chemosensory receptors in the olfactory epithelium". Nature. 442 (7103): 645–650. Bibcode:2006Natur.442..645L. doi:10.1038/nature05066. PMID 16878137. S2CID 2864195.
^ abcdefghijk"Trace amine receptor: Introduction". International Union of Basic and Clinical Pharmacology. Retrieved 15 February 2014. Importantly, three ligands identified activating mouse Taars are natural components of mouse urine, a major source of social cues in rodents. Mouse Taar4 recognizes β-phenylethylamine, a compound whose elevation in urine is correlated with increases in stress and stress responses in both rodents and humans. Both mouse Taar3 and Taar5 detect compounds (isoamylamine and trimethylamine, respectively) that are enriched in male versus female mouse urine. Isoamylamine in male urine is reported to act as a pheromone, accelerating puberty onset in female mice [34]. The authors suggest the Taar family has a chemosensory function that is distinct from odorant receptors with a role associated with the detection of social cues. ... The evolutionary pattern of the TAAR gene family is characterized by lineage-specific phylogenetic clustering [26,30,35]. These characteristics are very similar to those observed in the olfactory GPCRs and vomeronasal (V1R, V2R) GPCR gene families.
^ abBabusyte A, Kotthoff M, Fiedler J, Krautwurst D (March 2013). "Biogenic amines activate blood leukocytes via trace amine-associated receptors TAAR1 and TAAR2". Journal of Leukocyte Biology. 93 (3): 387–394. doi:10.1189/jlb.0912433. PMID 23315425.
^ ab"TAAR2". International Union of Basic and Clinical Pharmacology. Retrieved 15 May 2018. Primary Transduction Mechanisms Comments: TAAR2 is found to be coexpressed with Gα proteins. However, the transduction pathway of TAAR2 is yet to be determined.
^ abKhan MZ, Nawaz W (October 2016). "The emerging roles of human trace amines and human trace amine-associated receptors (hTAARs) in central nervous system". Biomedicine & Pharmacotherapy. 83: 439–449. doi:10.1016/j.biopha.2016.07.002. PMID 27424325.
^ abcWallrabenstein I, Singer M, Panten J, Hatt H, Gisselmann G (2015). "Timberol® Inhibits TAAR5-Mediated Responses to Trimethylamine and Influences the Olfactory Threshold in Humans". PLOS ONE. 10 (12): e0144704. Bibcode:2015PLoSO..1044704W. doi:10.1371/journal.pone.0144704. PMC4684214. PMID 26684881. While mice produce gender-specific amounts of urinary TMA levels and were attracted by TMA, this odor is repellent to rats and aversive to humans [19], indicating that there must be species-specific functions. ... Furthermore, a homozygous knockout of murine TAAR5 abolished the attraction behavior to TMA [19]. Thus, it is concluded that TAAR5 itself is sufficient to mediate a behavioral response at least in mice. ... Whether the TAAR5 activation by TMA elicits specific behavioral output like avoidance behavior in humans still needs to be examined.
^Offermanns, Stefan (2008). Walter Rosenthal (ed.). Encyclopedia of Molecular Pharmacology (2nd ed.). Berlin: Springer. pp. 1219–1222. ISBN978-3540389163.
^Wallrabenstein I, Kuklan J, Weber L, Zborala S, Werner M, Altmüller J, et al. (2013). "Human trace amine-associated receptor TAAR5 can be activated by trimethylamine". PLOS ONE. 8 (2): e54950. Bibcode:2013PLoSO...854950W. doi:10.1371/journal.pone.0054950. PMC3564852. PMID 23393561.
^Zhang J, Pacifico R, Cawley D, Feinstein P, Bozza T (February 2013). "Ultrasensitive detection of amines by a trace amine-associated receptor". The Journal of Neuroscience. 33 (7): 3228–3239. doi:10.1523/JNEUROSCI.4299-12.2013. PMC3711460. PMID 23407976. We show that [human TAAR5] 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).
^Dinter J, Mühlhaus J, Wienchol CL, Yi CX, Nürnberg D, Morin S, et al. (2015). "Inverse agonistic action of 3-iodothyronamine at the human trace amine-associated receptor 5". PLOS ONE. 10 (2): e0117774. Bibcode:2015PLoSO..1017774D. doi:10.1371/journal.pone.0117774. PMC4382497. PMID 25706283.
^ abIzquierdo C, Gómez-Tamayo JC, Nebel JC, Pardo L, Gonzalez A (January 2018). "Identifying human diamine sensors for death related putrescine and cadaverine molecules". PLOS Computational Biology. 14 (1): e1005945. Bibcode:2018PLSCB..14E5945I. doi:10.1371/journal.pcbi.1005945. PMC5783396. PMID 29324768.
^"TAAR6". International Union of Basic and Clinical Pharmacology. Retrieved 15 May 2018. Tissue Distribution Kidney, amygdala, hippocampus; Species: Human; Technique: RT-PCR ... Human brain tissues (with the level of expression descending from hippocampus, substantia nigra, amygdala, frontal cortex to basal ganglia), human fetal liver. Not detected in the cerebellum or placenta.; Species: Human; Technique: RT-PCR
^Vaganova AN, Kuvarzin SR, Sycheva AM, Gainetdinov RR (January 2022). "Deregulation of Trace Amine-Associated Receptors (TAAR) Expression and Signaling Mode in Melanoma". Biomolecules. 12 (1): 114. doi:10.3390/biom12010114. PMC8774021. PMID 35053262.
^Mühlhaus J, Dinter J, Nürnberg D, Rehders M, Depke M, Golchert J, et al. (November 2014). "Analysis of human TAAR8 and murine Taar8b mediated signaling pathways and expression profile". International Journal of Molecular Sciences. 15 (11): 20638–20655. doi:10.3390/ijms151120638. PMC4264187. PMID 25391046.
^Liberles SD (October 2015). "Trace amine-associated receptors: ligands, neural circuits, and behaviors". Current Opinion in Neurobiology. 34: 1–7. doi:10.1016/j.conb.2015.01.001. PMC4508243. PMID 25616211.
^"TAAR9". International Union of Basic and Clinical Pharmacology. Retrieved 15 May 2018. Tissue Distribution Comments ... No expression of TAAR9 was detected by RT-PCR in the Grueneberg ganglion [2]. TAAR9 expression was not detected by Northern blot analysis in thalamus, amygdala, midbrain, hippocampus, putamen, caudate, frontal cortex, pons, prostate, stomach, heart, bladder, small intestine, colon or uterus [4].
^Heffernan ML, Herman LW, Brown S, Jones PG, Shao L, Hewitt MC, et al. (January 2022). "Ulotaront: A TAAR1 Agonist for the Treatment of Schizophrenia". ACS Medicinal Chemistry Letters. 13 (1): 92–98. doi:10.1021/acsmedchemlett.1c00527. PMC8762745. PMID 35047111.
^"Sunovion: creating therapies to help transform people's lives". www.sunovion.com. Retrieved 4 June 2022.
^"Sunovion and PsychoGenics Announce that SEP-363856 Has Received FDA Breakthrough Therapy Designation for the Treatment of People with Schizophrenia". news.sunovion.com. Retrieved 4 June 2022.
External linksedit
"Trace Amine Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
April 13, 2024
trace, amine, associated, receptor, taar, redirects, here, other, uses, taar, string, instrument, taar, film, taars, sometimes, referred, trace, amine, receptors, tars, class, protein, coupled, receptors, that, were, discovered, 2001, taar1, first, functional,. TAAR redirects here For other uses of Taar see Tar string instrument and Taar film 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 TAAR1 the first of six functional human TAARs has gained considerable interest in academic and proprietary pharmaceutical research due to its role as the endogenous receptor for the trace amines phenethylamine tyramine and tryptamine metabolic derivatives of the amino acids phenylalanine tyrosine and tryptophan respectively ephedrine as well as the synthetic psychostimulants amphetamine methamphetamine and methylenedioxymethamphetamine MDMA ecstasy 3 4 5 6 7 8 In 2004 it was shown that mammalian TAAR1 is also a receptor for thyronamines decarboxylated and deiodinated relatives of thyroid hormones 5 TAAR2 TAAR9 function as olfactory receptors for volatile amine odorants in vertebrates 9 Contents 1 Animal TAAR complement 2 Human trace amine associated receptors 2 1 Disease links and clinical significance 3 See also 4 References 5 External linksAnimal TAAR complement editThe following is a list of the TAARs contained in selected animal genomes 10 11 Human 6 genes TAAR1 TAAR2 TAAR5 TAAR6 TAAR8 TAAR9 and 3 pseudogenes TAAR3 TAAR4P TAAR7P 12 Chimpanzee 3 genes and 6 pseudogenes Mouse 15 genes and 1 pseudogene Rat 17 genes and 2 pseudogenes Zebrafish 112 genes and 4 pseudogenes Frog 3 genes and 0 pseudogenes Medaka 25 genes and 1 pseudogenes Stickleback 25 genes and 1 pseudogenesHuman trace amine associated receptors editSix human trace amine associated receptors hTAARs hTAAR1 hTAAR2 hTAAR5 hTAAR6 hTAAR8 and hTAAR9 have been identified and partially characterized The table below contains summary information from literature reviews pharmacology databases and supplementary primary research articles on the expression profiles signal transduction mechanisms ligands and physiological functions of these receptors The pharmacology and molecular biology of human trace amine associated receptors TAARsubtype Priornames Signaltransduction Expressionprofile Known or putative function in humans note 1 Known ligands SourceshTAAR1 TA1TAR1 Gs Gq GIRKs b arrestin 2 CNS brain widespread spinal cordPeriphery pancreatic b cells stomach duodenum intestines leukocytes elsewhere note 2 CNS modulation of monoamine glutamate neurotransmission CNS regulation of cognitive processes amp mood states Periphery leukocyte chemotaxis Periphery regulation of GI hormone release amp blood glucose Regulation of satiety amp body weight Trace amines e g tyramine PEA NMPEA Monoamine neurotransmitters e g dopamine Amphetamine and some structural analogs 3 13 15 16 hTAAR2 note 3 GPR58 Golf other G protein coupling unknown note 4 CNS brain restricted note 5 Periphery olfactory epithelium intestines heart testes leukocytes Periphery leukocyte chemotaxis Olfaction chemoreceptor for volatile odorants note 6 9 13 15 16 17 18 TAAR3 GPR57 N A N A Pseudogene in humans N A N A 12 13 15 TAAR4 TA2 N A N A Pseudogene in humans N A N A 12 13 15 hTAAR5 PNR Gs Golf Gq G12 13 CNS brain restricted spinal cordPeriphery olfactory epithelium intestines testes leukocytes Olfaction chemoreceptor for volatile amp foul odorants note 6 Agonists trimethylamine N N DMEA Inverse agonists 3 iodothyronamine 9 13 15 20 21 22 23 hTAAR6 TA4TAR4 Golf other G protein coupling unknown CNS brainPeriphery olfactory epithelium intestines testes leukocytes kidneys Olfaction chemoreceptor for volatile odorants note 6 Agonists putrescine and cadaverine 24 9 13 15 25 TAAR7 N A N A Pseudogene in humans N A N A 9 13 15 hTAAR8 TA5GPR102 Golf Gi o CNS brainPeriphery olfactory epithelium melanocytes 26 stomach intestines heart testes leukocytes kidneys lungs muscle spleen Olfaction chemoreceptor for volatile odorants note 6 Agonists putrescine and cadaverine 24 9 13 15 27 hTAAR9 note 7 TA3TAR3 Golf other G protein coupling unknown CNS spinal cordPeriphery olfactory epithelium intestines leukocytes pituitary gland skeletal muscle spleen Olfaction chemoreceptor for volatile odorants note 6 Agonist N Methyl piperidine CAS 626 67 5 28 9 13 15 29 Notes As of December 2017 update the functions of hTAAR2 hTAAR5 hTAAR6 hTAAR8 and hTAAR9 in the CNS and peripheral tissues outside the olfactory epithelium have not been determined 13 hTAAR1 is the only TAAR subtype that is not expressed within the human olfactory epithelium 9 14 Hence unlike all other human trace amine associated receptors hTAAR1 does not function as an olfactory receptor in humans 9 14 hTAAR2 is a non functional receptor in 10 15 of Asians due to the occurrence of a single nucleotide polymorphism involving a premature stop codon in the human TAAR2 gene 12 13 hTAAR2 has been found to be coexpressed with Ga proteins however its exact signal transduction mechanisms have not yet been established 13 17 hTAAR2 expression has been observed in the human cerebellum 18 a b c d e In humans and other animals TAARs that are expressed in the olfactory epithelium function as olfactory receptors that detect volatile amine odorants including certain pheromones 9 15 these TAARs putatively function as a class of pheromone receptors involved in the olfactive detection of social cues 9 15 A review of studies involving non human animals indicated that TAARs in the olfactory epithelium can mediate attractive or aversive behavioral responses to an agonist 9 This review also noted that the behavioral response evoked by a TAAR can vary across species 9 For example TAAR5 mediates attraction to trimethylamine in mice and aversion to trimethylamine in rats 9 In humans hTAAR5 presumably mediates aversion to trimethylamine which is known to act as an hTAAR5 agonist and to possess a foul fishy odor that is aversive to humans 9 19 however hTAAR5 is not the only olfactory receptor that is responsible for trimethylamine olfaction in humans 9 19 As of December 2015 update hTAAR5 mediated trimethylamine aversion has not been examined in published research 19 hTAAR9 is a functional receptor in most individuals but a loss of function mutation specifically a polymorphic premature stop codon in the human TAAR9 gene occurs in 10 30 of individuals 12 13 Disease links and clinical significance edit Ulotaront SEP 363856 is a TAAR1 agonist in phase 3 clinical trials for schizophrenia and earlier trials for Parkinson s Disease psychosis The medicine has obtained Breakthrough designation from the US FDA 30 31 32 This section needs expansion with coverage of relevant material from this review 13 You can help by adding to it March 2018 See also editOlfactory receptor Odorant Pheromone Pheromone receptor Psychostimulant Thyronamine Trace amineReferences edit Borowsky B Adham N Jones KA Raddatz R Artymyshyn R Ogozalek KL et al July 2001 Trace amines identification of a family of mammalian G protein coupled receptors Proceedings of the National Academy of Sciences of the United States of America 98 16 8966 8971 doi 10 1073 pnas 151105198 PMC 55357 PMID 11459929 Bunzow JR Sonders MS Arttamangkul S Harrison LM Zhang G Quigley DI et al December 2001 Amphetamine 3 4 methylenedioxymethamphetamine lysergic acid diethylamide and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor Molecular Pharmacology 60 6 1181 1188 doi 10 1124 mol 60 6 1181 PMID 11723224 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 Journal of Neurochemistry 116 2 164 176 doi 10 1111 j 1471 4159 2010 07109 x PMC 3005101 PMID 21073468 Lam VM Espinoza S Gerasimov AS Gainetdinov RR Salahpour A September 2015 In vivo pharmacology of Trace Amine Associated Receptor 1 European Journal of Pharmacology 763 Pt B 136 142 doi 10 1016 j ejphar 2015 06 026 PMID 26093041 a b Scanlan TS Suchland KL Hart ME Chiellini G Huang Y Kruzich PJ et al June 2004 3 Iodothyronamine is an endogenous and rapid acting derivative of thyroid hormone Nature Medicine 10 6 638 642 doi 10 1038 nm1051 PMID 15146179 S2CID 2389946 Lindemann L Hoener MC May 2005 A renaissance in trace amines inspired by a novel GPCR family Trends in Pharmacological Sciences 26 5 274 281 doi 10 1016 j tips 2005 03 007 PMID 15860375 Hart ME Suchland KL Miyakawa M Bunzow JR Grandy DK Scanlan TS February 2006 Trace amine associated receptor agonists synthesis and evaluation of thyronamines and related analogues Journal of Medicinal Chemistry 49 3 1101 1112 doi 10 1021 jm0505718 PMID 16451074 Grandy DK December 2007 Trace amine associated receptor 1 Family archetype or iconoclast Pharmacology amp Therapeutics 116 3 355 390 doi 10 1016 j pharmthera 2007 06 007 PMC 2767338 PMID 17888514 a b c d e f g h i j k l m n o p Liberles SD October 2015 Trace amine associated receptors ligands neural circuits and behaviors Current Opinion in Neurobiology 34 1 7 doi 10 1016 j conb 2015 01 001 PMC 4508243 PMID 25616211 Roles for another receptor are supported by TAAR5 independent trimethylamine anosmias in humans 32 Several TAARs detect volatile and aversive amines but the olfactory system is capable of discarding ligand based or function based constraints on TAAR evolution Particular TAARs have mutated to recognize new ligands with almost an entire teleost clade losing the canonical amine recognition motif Furthermore while some TAARs detect aversive odors TAAR mediated behaviors can vary across species The ability of particular TAARs to mediate aversion and attraction behavior provides an exciting opportunity for mechanistic unraveling of odor valence encoding Figure 2 Table of ligands expression patterns and species specific behavioral responses for each TAAR Hussain A Saraiva LR Korsching SI March 2009 Positive Darwinian selection and the birth of an olfactory receptor clade in teleosts Proceedings of the National Academy of Sciences of the United States of America 106 11 4313 4318 Bibcode 2009PNAS 106 4313H doi 10 1073 pnas 0803229106 PMC 2657432 PMID 19237578 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 Pharmacological Reviews 61 1 1 8 doi 10 1124 pr 109 001107 PMC 2830119 PMID 19325074 a b c d e Davenport AP Alexander SP Sharman JL Pawson AJ Benson HE Monaghan AE et al July 2013 International Union of Basic and Clinical Pharmacology LXXXVIII G protein coupled receptor list recommendations for new pairings with cognate ligands Pharmacological Reviews 65 3 967 986 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 a b c d e f g h i j k l m n Berry MD Gainetdinov RR Hoener MC Shahid M December 2017 Pharmacology of human trace amine associated receptors Therapeutic opportunities and challenges Pharmacology amp Therapeutics 180 161 180 doi 10 1016 j pharmthera 2017 07 002 PMID 28723415 a b Liberles SD Buck LB August 2006 A second class of chemosensory receptors in the olfactory epithelium Nature 442 7103 645 650 Bibcode 2006Natur 442 645L doi 10 1038 nature05066 PMID 16878137 S2CID 2864195 a b c d e f g h i j k Trace amine receptor Introduction International Union of Basic and Clinical Pharmacology Retrieved 15 February 2014 Importantly three ligands identified activating mouse Taars are natural components of mouse urine a major source of social cues in rodents Mouse Taar4 recognizes b phenylethylamine a compound whose elevation in urine is correlated with increases in stress and stress responses in both rodents and humans Both mouse Taar3 and Taar5 detect compounds isoamylamine and trimethylamine respectively that are enriched in male versus female mouse urine Isoamylamine in male urine is reported to act as a pheromone accelerating puberty onset in female mice 34 The authors suggest the Taar family has a chemosensory function that is distinct from odorant receptors with a role associated with the detection of social cues The evolutionary pattern of the TAAR gene family is characterized by lineage specific phylogenetic clustering 26 30 35 These characteristics are very similar to those observed in the olfactory GPCRs and vomeronasal V1R V2R GPCR gene families 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 Journal of Leukocyte Biology 93 3 387 394 doi 10 1189 jlb 0912433 PMID 23315425 a b TAAR2 International Union of Basic and Clinical Pharmacology Retrieved 15 May 2018 Primary Transduction MechanismsComments TAAR2 is found to be coexpressed with Ga proteins However the transduction pathway of TAAR2 is yet to be determined a b Khan MZ Nawaz W October 2016 The emerging roles of human trace amines and human trace amine associated receptors hTAARs in central nervous system Biomedicine amp Pharmacotherapy 83 439 449 doi 10 1016 j biopha 2016 07 002 PMID 27424325 a b c Wallrabenstein I Singer M Panten J Hatt H Gisselmann G 2015 Timberol Inhibits TAAR5 Mediated Responses to Trimethylamine and Influences the Olfactory Threshold in Humans PLOS ONE 10 12 e0144704 Bibcode 2015PLoSO 1044704W doi 10 1371 journal pone 0144704 PMC 4684214 PMID 26684881 While mice produce gender specific amounts of urinary TMA levels and were attracted by TMA this odor is repellent to rats and aversive to humans 19 indicating that there must be species specific functions Furthermore a homozygous knockout of murine TAAR5 abolished the attraction behavior to TMA 19 Thus it is concluded that TAAR5 itself is sufficient to mediate a behavioral response at least in mice Whether the TAAR5 activation by TMA elicits specific behavioral output like avoidance behavior in humans still needs to be examined Offermanns Stefan 2008 Walter Rosenthal ed Encyclopedia of Molecular Pharmacology 2nd ed Berlin Springer pp 1219 1222 ISBN 978 3540389163 Wallrabenstein I Kuklan J Weber L Zborala S Werner M Altmuller J et al 2013 Human trace amine associated receptor TAAR5 can be activated by trimethylamine PLOS ONE 8 2 e54950 Bibcode 2013PLoSO 854950W doi 10 1371 journal pone 0054950 PMC 3564852 PMID 23393561 Zhang J Pacifico R Cawley D Feinstein P Bozza T February 2013 Ultrasensitive detection of amines by a trace amine associated receptor The Journal of Neuroscience 33 7 3228 3239 doi 10 1523 JNEUROSCI 4299 12 2013 PMC 3711460 PMID 23407976 We show that human TAAR5 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 Dinter J Muhlhaus J Wienchol CL Yi CX Nurnberg D Morin S et al 2015 Inverse agonistic action of 3 iodothyronamine at the human trace amine associated receptor 5 PLOS ONE 10 2 e0117774 Bibcode 2015PLoSO 1017774D doi 10 1371 journal pone 0117774 PMC 4382497 PMID 25706283 a b Izquierdo C Gomez Tamayo JC Nebel JC Pardo L Gonzalez A January 2018 Identifying human diamine sensors for death related putrescine and cadaverine molecules PLOS Computational Biology 14 1 e1005945 Bibcode 2018PLSCB 14E5945I doi 10 1371 journal pcbi 1005945 PMC 5783396 PMID 29324768 TAAR6 International Union of Basic and Clinical Pharmacology Retrieved 15 May 2018 Tissue Distribution Kidney amygdala hippocampus Species Human Technique RT PCR Human brain tissues with the level of expression descending from hippocampus substantia nigra amygdala frontal cortex to basal ganglia human fetal liver Not detected in the cerebellum or placenta Species Human Technique RT PCR Vaganova AN Kuvarzin SR Sycheva AM Gainetdinov RR January 2022 Deregulation of Trace Amine Associated Receptors TAAR Expression and Signaling Mode in Melanoma Biomolecules 12 1 114 doi 10 3390 biom12010114 PMC 8774021 PMID 35053262 Muhlhaus J Dinter J Nurnberg D Rehders M Depke M Golchert J et al November 2014 Analysis of human TAAR8 and murine Taar8b mediated signaling pathways and expression profile International Journal of Molecular Sciences 15 11 20638 20655 doi 10 3390 ijms151120638 PMC 4264187 PMID 25391046 Liberles SD October 2015 Trace amine associated receptors ligands neural circuits and behaviors Current Opinion in Neurobiology 34 1 7 doi 10 1016 j conb 2015 01 001 PMC 4508243 PMID 25616211 TAAR9 International Union of Basic and Clinical Pharmacology Retrieved 15 May 2018 Tissue Distribution Comments No expression of TAAR9 was detected by RT PCR in the Grueneberg ganglion 2 TAAR9 expression was not detected by Northern blot analysis in thalamus amygdala midbrain hippocampus putamen caudate frontal cortex pons prostate stomach heart bladder small intestine colon or uterus 4 Heffernan ML Herman LW Brown S Jones PG Shao L Hewitt MC et al January 2022 Ulotaront A TAAR1 Agonist for the Treatment of Schizophrenia ACS Medicinal Chemistry Letters 13 1 92 98 doi 10 1021 acsmedchemlett 1c00527 PMC 8762745 PMID 35047111 Sunovion creating therapies to help transform people s lives www sunovion com Retrieved 4 June 2022 Sunovion and PsychoGenics Announce that SEP 363856 Has Received FDA Breakthrough Therapy Designation for the Treatment of People with Schizophrenia news sunovion com Retrieved 4 June 2022 External links edit Trace Amine Receptors IUPHAR Database of Receptors and Ion Channels International Union of Basic and Clinical Pharmacology Retrieved from https en wikipedia org w index php title Trace amine associated receptor amp oldid 1210186144 Human trace amine associated receptors, wikipedia, wiki, book, books, library,
