Trace amine-associated receptor

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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

Animal TAAR complement

The following is a list of the TAARs contained in selected animal genomes: [10] [11]

Human trace amine-associated receptors

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
TAAR
subtype		Prior
names		 Signal
transduction 		Expression
profile 		Known or putative function in humans [note 1] Known ligands Sources
hTAAR1 TA1
TAR1		 Gs , Gq ,
GIRKs,
β-arrestin 2 		CNS:  brain  (widespread), spinal cord
Periphery:  pancreatic β-cells, stomach, duodenum, intestines, leukocytes, elsewhere [note 2] 		 • CNS:  modulation of monoamine/glutamate neurotransmission
 •CNS: regulation of cognitive processes & mood states
 •Periphery:  leukocyte chemotaxis
 •Periphery: regulation of GI hormone release & blood glucose
 •Regulation of satiety & 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 GPR57N/AN/A Pseudogene in humans – N/AN/A [12] [13]
[15]
TAAR4TA2N/AN/APseudogene in humans – N/AN/A [12] [13]
[15]
hTAAR5 PNR Gs , Golf ,
Gq , G12/13 		CNS: brain (restricted),
spinal cord
Periphery: olfactory epithelium, intestines, testes, leukocytes		 •Olfaction: chemoreceptor for volatile & foul odorants [note 6]  •Agonists: trimethylamine, N,N-DMEA
 •Inverse agonists: 3-iodothyronamine 		[9] [13]
[15] [20]
[21] [22]
[23]
hTAAR6 TA4
TAR4		 Golf , other G protein  coupling unknownCNS: brain
Periphery: olfactory epithelium, intestines, testes, leukocytes, kidneys 		 •Olfaction: chemoreceptor for volatile odorants [note 6]  •Agonists: putrescine and cadaverine [24] [9] [13]
[15] [25]
TAAR7–N/AN/APseudogene in humans – N/AN/A [9] [13]
[15]
hTAAR8 TA5
GPR102		 Golf , Gi/o CNS: brain
Periphery: 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] 		TA3
TAR3		 Golf , other G protein  coupling unknownCNS: spinal cord
Periphery: 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
  1. ↑ As of December 2017, the functions of hTAAR2, hTAAR5, hTAAR6, hTAAR8, and hTAAR9 in the CNS and peripheral tissues outside the olfactory epithelium have not been determined. [13]
  2. ↑ 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]
  3. ↑ 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]
  4. ↑ hTAAR2 has been found to be coexpressed with Gα proteins, however its exact signal transduction mechanisms have not yet been established. [13] [17]
  5. ↑ hTAAR2 expression has been observed in the human cerebellum. [18]
  6. 1 2 3 4 5 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, hTAAR5-mediated trimethylamine aversion has not been examined in published research. [19]
  7. ↑ 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]

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]

See also

Related Research Articles

<span class="mw-page-title-main">Pheromone</span> Secreted or excreted chemical factor that triggers a social response in members of the same species

A pheromone is a secreted or excreted chemical factor that triggers a social response in members of the same species. Pheromones are chemicals capable of acting like hormones outside the body of the secreting individual, to affect the behavior of the receiving individuals. There are alarm pheromones, food trail pheromones, sex pheromones, and many others that affect behavior or physiology. Pheromones are used by many organisms, from basic unicellular prokaryotes to complex multicellular eukaryotes. Their use among insects has been particularly well documented. In addition, some vertebrates, plants and ciliates communicate by using pheromones. The ecological functions and evolution of pheromones are a major topic of research in the field of chemical ecology.

<span class="mw-page-title-main">Monoamine neurotransmitter</span> Monoamine that acts as a neurotransmitter or neuromodulator

Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin.

<span class="mw-page-title-main">Phenethylamine</span> Organic compound, a stimulant in humans

Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace amine-associated receptor 1 (TAAR1) and inhibiting vesicular monoamine transporter 2 (VMAT2) in monoamine neurons. To a lesser extent, it also acts as a neurotransmitter in the human central nervous system. In mammals, phenethylamine is produced from the amino acid L-phenylalanine by the enzyme aromatic L-amino acid decarboxylase via enzymatic decarboxylation. In addition to its presence in mammals, phenethylamine is found in many other organisms and foods, such as chocolate, especially after microbial fermentation.

<span class="mw-page-title-main">Tryptamine</span> Metabolite of the amino acid tryptophan

Tryptamine is an indolamine metabolite of the essential amino acid, tryptophan. The chemical structure is defined by an indole—a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the first one being the heterocyclic nitrogen). The structure of tryptamine is a shared feature of certain aminergic neuromodulators including melatonin, serotonin, bufotenin and psychedelic derivatives such as dimethyltryptamine (DMT), psilocybin, psilocin and others. Tryptamine has been shown to activate trace amine-associated receptors expressed in the mammalian brain, and regulates the activity of dopaminergic, serotonergic and glutamatergic systems. In the human gut, symbiotic bacteria convert dietary tryptophan to tryptamine, which activates 5-HT4 receptors and regulates gastrointestinal motility. Multiple tryptamine-derived drugs have been developed to treat migraines, while trace amine-associated receptors are being explored as a potential treatment target for neuropsychiatric disorders.

A biogenic amine is a biogenic substance with one or more amine groups. They are basic nitrogenous compounds formed mainly by decarboxylation of amino acids or by amination and transamination of aldehydes and ketones. Biogenic amines are organic bases with low molecular weight and are synthesized by microbial, vegetable and animal metabolisms. In food and beverages they are formed by the enzymes of raw material or are generated by microbial decarboxylation of amino acids.

<span class="mw-page-title-main">Tyramine</span> Chemical compound

Tyramine, also known under several other names, is a naturally occurring trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent. Notably, it is unable to cross the blood-brain barrier, resulting in only non-psychoactive peripheral sympathomimetic effects following ingestion. A hypertensive crisis can result, however, from ingestion of tyramine-rich foods in conjunction with the use of monoamine oxidase inhibitors (MAOIs).

<span class="mw-page-title-main">Olfactory receptor</span> Chemoreceptors expressed in cell membranes of olfactory receptor neurons

Olfactory receptors (ORs), also known as odorant receptors, are chemoreceptors expressed in the cell membranes of olfactory receptor neurons and are responsible for the detection of odorants which give rise to the sense of smell. Activated olfactory receptors trigger nerve impulses which transmit information about odor to the brain. In vertebrates, these receptors are members of the class A rhodopsin-like family of G protein-coupled receptors (GPCRs). The olfactory receptors form a multigene family consisting of around 400 genes in humans and 1400 genes in mice. In insects, olfactory receptors are members of an unrelated group of ligand-gated ion channels.

<span class="mw-page-title-main">Trimethylamine</span> Chemical compound responsible for rotten fish odor

Trimethylamine (TMA) is an organic compound with the formula N(CH3)3. It is a trimethylated derivative of ammonia. TMA is widely used in industry. At higher concentrations it has an ammonia-like odor, and can cause necrosis of mucous membranes on contact. At lower concentrations, it has a "fishy" odor, the odor associated with rotting fish.

<span class="mw-page-title-main">Trace amine</span> Amine receptors in the mammalian brain

Trace amines are an endogenous group of trace amine-associated receptor 1 (TAAR1) agonists – and hence, monoaminergic neuromodulators – that are structurally and metabolically related to classical monoamine neurotransmitters. Compared to the classical monoamines, they are present in trace concentrations. They are distributed heterogeneously throughout the mammalian brain and peripheral nervous tissues and exhibit high rates of metabolism. Although they can be synthesized within parent monoamine neurotransmitter systems, there is evidence that suggests that some of them may comprise their own independent neurotransmitter systems.

Dopamine receptor D<sub>2</sub> Main receptor for most antipsychotic drugs

Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene. After work from Paul Greengard's lab had suggested that dopamine receptors were the site of action of antipsychotic drugs, several groups, including those of Solomon Snyder and Philip Seeman used a radiolabeled antipsychotic drug to identify what is now known as the dopamine D2 receptor. The dopamine D2 receptor is the main receptor for most antipsychotic drugs. The structure of DRD2 in complex with the atypical antipsychotic risperidone has been determined.

<span class="mw-page-title-main">TAAR2</span> Protein-coding gene in the species Homo sapiens

Trace amine-associated receptor 2 (TAAR2), formerly known as G protein-coupled receptor 58 (GPR58), is a protein that in humans is encoded by the TAAR2 gene. TAAR2 is coexpressed with Gα proteins; however, as of February 2017, its signal transduction mechanisms have not been determined.

<span class="mw-page-title-main">TAAR3</span> Human pseudogene

Putative trace amine-associated receptor 3 (TAAR3) is a human pseudogene with the gene symbol TAAR3P. In other species such as mice, TAAR3 is a functional protein-coding gene that encodes a trace amine-associated receptor protein.

<span class="mw-page-title-main">TAAR6</span> Protein and coding gene in humans

Trace amine associated receptor 6, also known as TAAR6, is a protein which in humans is encoded by the TAAR6 gene.

<span class="mw-page-title-main">TAAR5</span> Protein-coding gene in the species Homo sapiens

Trace amine-associated receptor 5 is a protein that in humans is encoded by the TAAR5 gene. In vertebrates, TAAR5 is expressed in the olfactory epithelium.

<span class="mw-page-title-main">TAAR1</span> Protein-coding gene in the species Homo sapiens

Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the TAAR1 gene. TAAR1 is an intracellular amine-activated Gs-coupled and Gq-coupled G protein-coupled receptor (GPCR) that is primarily expressed in several peripheral organs and cells, astrocytes, and in the intracellular milieu within the presynaptic plasma membrane of monoamine neurons in the central nervous system (CNS). TAAR1 was discovered in 2001 by two independent groups of investigators, Borowski et al. and Bunzow et al. TAAR1 is one of six functional human trace amine-associated receptors, which are so named for their ability to bind endogenous amines that occur in tissues at trace concentrations. TAAR1 plays a significant role in regulating neurotransmission in dopamine, norepinephrine, and serotonin neurons in the CNS; it also affects immune system and neuroimmune system function through different mechanisms.

<span class="mw-page-title-main">TAAR9</span> Protein-coding gene in the species Homo sapiens

Trace amine-associated receptor 9 is a protein that in humans is encoded by the TAAR9 gene.

<span class="mw-page-title-main">3-Methoxytyramine</span> Chemical compound

3-Methoxytyramine (3-MT), also known as 3-methoxy-4-hydroxyphenethylamine, is a human trace amine that occurs as a metabolite of the neurotransmitter dopamine. It is formed by the introduction of a methyl group to dopamine by the enzyme catechol-O-methyl transferase (COMT). 3-MT can be further metabolized by the enzyme monoamine oxidase (MAO) to form homovanillic acid (HVA), which is then typically excreted in the urine.

<span class="mw-page-title-main">RO5166017</span> Chemical compound

RO-5166017 is a drug developed by Hoffmann-La Roche which acts as a potent and selective agonist for the trace amine-associated receptor 1, with no significant activity at other targets. This is important for the study of the TAAR1 receptor, as while numerous other compounds are known which act as TAAR1 agonists, such as methamphetamine, MDMA and 3-iodothyronamine, all previously known TAAR1 agonists are either weak and rapidly metabolized, or have strong pharmacological activity at other targets, making it very difficult to assess which effects are due to TAAR1 activation. The discovery of RO-5166017 allows purely TAAR1 mediated effects to be studied, and in animal studies it was shown to prevent stress-induced hyperthermia and block dopamine-dependent hyperlocomotion, as well as blocking the hyperactivity which would normally be induced by an NMDA antagonist. The experiment was done in dopamine transporter knockout mice, and since TAAR1 affects the dopamine transporter, the results could be very different in humans.

<span class="mw-page-title-main">EPPTB</span> Chemical compound

EPPTB (RO-5212773) is a drug developed by Hoffmann-La Roche which acts as a potent and selective inverse agonist of trace amine-associated receptor 1 (TAAR1), with no significant activity at other targets. EPPTB is one of the first selective antagonists developed for TAAR1, and has been used to demonstrate an important role for TAAR1 in regulation of dopaminergic signalling in the limbic system. Although EPPTB has high affinity for the mouse TAAR1, it has much lower affinity for rat and human TAAR1, which limits its use in research. While the human and mouse forms of TAAR1 have similar functions and bind similar ligands, the actual binding affinities of individual ligands often vary significantly between the two versions of the receptor.

<span class="mw-page-title-main">Copulation (zoology)</span> Animal sexual reproductive act in which a male introduces sperm into the females body

In zoology, copulation is animal sexual behavior in which a male introduces sperm into the female's body, especially directly into her reproductive tract. This is an aspect of mating. Many animals that live in water use external fertilization, whereas internal fertilization may have developed from a need to maintain gametes in a liquid medium in the Late Ordovician epoch. Internal fertilization with many vertebrates occurs via cloacal copulation, known as cloacal kiss, while most mammals copulate vaginally, and many basal vertebrates reproduce sexually with external fertilization.

References

  1. ↑ 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.
  2. ↑ 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.
  3. 1 2 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.
  4. ↑ 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.
  5. 1 2 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ Grandy DK (December 2007). "Trace amine-associated receptor 1-Family archetype or iconoclast?". Pharmacology & Therapeutics. 116 (3): 355–390. doi:10.1016/j.pharmthera.2007.06.007. PMC   2767338 . PMID   17888514.
  9. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 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
  10. ↑ 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.
  11. ↑ 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.
  12. 1 2 3 4 5 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).
  13. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Berry 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.
  14. 1 2 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.
  15. 1 2 3 4 5 6 7 8 9 10 11 "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.
  16. 1 2 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.
  17. 1 2 "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.
  18. 1 2 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 & Pharmacotherapy. 83: 439–449. doi:10.1016/j.biopha.2016.07.002. PMID   27424325.
  19. 1 2 3 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.
  20. ↑ Offermanns, Stefan (2008). Walter Rosenthal (ed.). Encyclopedia of Molecular Pharmacology (2nd ed.). Berlin: Springer. pp.  1219–1222. ISBN   978-3540389163.
  21. ↑ 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 . PMC   3564852 . PMID   23393561.
  22. ↑ 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).
  23. ↑ 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 . PMC   4382497 . PMID   25706283.
  24. 1 2 Izquierdo 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 . PMC   5783396 . PMID   29324768.
  25. ↑ "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
  26. ↑ 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.
  27. ↑ 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 . PMC   4264187 . PMID   25391046.
  28. ↑ 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.
  29. ↑ "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].
  30. ↑ 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.
  31. ↑ "Sunovion: creating therapies to help transform people's lives". www.sunovion.com. Retrieved 4 June 2022.
  32. ↑ "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.
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