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TA1 receptor

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Target not currently curated in GtoImmuPdb

Target id: 364

Nomenclature: TA1 receptor

Family: Trace amine receptor

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 339 6q23.2 TAAR1 trace amine associated receptor 1 6,8
Mouse 7 332 10 A4 Taar1 trace amine-associated receptor 1 8
Rat 7 332 1p12 Taar1 trace-amine-associated receptor 1 6,46
Previous and Unofficial Names Click here for help
TAR1 | TaR-1 | trace amine receptor 1 | TRAR1
Database Links Click here for help
Specialist databases
GPCRdb taar1_human (Hs), taar1_mouse (Mm), taar1_rat (Rn)
Other databases
Alphafold Q96RJ0 (Hs), Q923Y8 (Mm), Q923Y9 (Rn)
ChEMBL Target CHEMBL5857 (Hs), CHEMBL4908 (Mm), CHEMBL3833 (Rn)
DrugBank Target Q96RJ0 (Hs)
Ensembl Gene ENSG00000146399 (Hs), ENSMUSG00000056379 (Mm), ENSRNOG00000016073 (Rn)
Entrez Gene 134864 (Hs), 111174 (Mm), 113914 (Rn)
Human Protein Atlas ENSG00000146399 (Hs)
KEGG Gene hsa:134864 (Hs), mmu:111174 (Mm), rno:113914 (Rn)
OMIM 609333 (Hs)
Pharos Q96RJ0 (Hs)
RefSeq Nucleotide NM_138327 (Hs), NM_053205 (Mm), NM_134328 (Rn)
RefSeq Protein NP_612200 (Hs), NP_444435 (Mm), NP_599155 (Rn)
UniProtKB Q96RJ0 (Hs), Q923Y8 (Mm), Q923Y9 (Rn)
Wikipedia TAAR1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Cryo-EM structure of the methamphetamine-TA1 receptor complex
PDB Id:  8W87
Ligand:  methamphetamine
Resolution:  2.8Å
Species:  Human
References:  31
Image of receptor 3D structure from RCSB PDB
Description:  Cryo-EM structure of the RO5256390-TA1 receptor complex
PDB Id:  8W8A
Ligand:  RO5256390
Resolution:  2.8Å
Species:  Human
References:  31
Image of receptor 3D structure from RCSB PDB
Description:  Cryo-EM structure of the SEP-363856-bound TA1 receptor-Gs complex
PDB Id:  8W88
Ligand:  ulotaront
Resolution:  2.6Å
Species:  Human
References:  31
Natural/Endogenous Ligands Click here for help
dopamine
3-iodothyronamine
octopamine
β-phenylethylamine
tyramine
Comments: Tyramine is the most potent endogenous agonist
Potency order of endogenous ligands
tyramine > β-phenylethylamine > octopamine = dopamine  [6]

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Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]tyramine Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Full agonist 7.7 pKd 6
⤷ pKd 7.7 (Kd 2x10-8 M) [6]
RO5166017 Small molecule or natural product Mm Partial agonist 8.7 pKi 49
⤷ pKi 8.7 (Ki 1.9x10-9 M) [49]
RO5166017 Small molecule or natural product Rn Full agonist 8.6 pKi 49
⤷ pKi 8.6 (Ki 2.7x10-9 M) [49]
RO5166017 Small molecule or natural product Hs Full agonist 7.5 pKi 49
⤷ pKi 7.5 (Ki 3.1x10-8 M) [49]
tyramine Small molecule or natural product Ligand is endogenous in the given species Ligand has a PDB structure Rn Full agonist 7.2 pKi 7
⤷ pKi 7.2 (Ki 7x10-8 M) [7]
tyramine Small molecule or natural product Ligand is endogenous in the given species Ligand has a PDB structure Mm Agonist 6.4 pKi 7
⤷ pKi 6.4 (Ki 4.04x10-7 M) [7]
RO5166017 Small molecule or natural product Mm Partial agonist 8.5 pEC50 49
⤷ pEC50 8.5 (EC50 3.3x10-9 M) [49]
RO5166017 Small molecule or natural product Rn Full agonist 7.9 pEC50 49
⤷ pEC50 7.9 (EC50 1.4x10-8 M) [49]
3-iodothyronamine Small molecule or natural product Ligand is endogenous in the given species Rn Full agonist 7.5 – 7.9 pEC50 22,52,60
⤷ pEC50 7.5 – 7.9 [22,52,60]
dexamfetamine Small molecule or natural product Approved drug Ligand has a PDB structure Mm Full agonist 6.7 – 8.7 pEC50 46,63
⤷ pEC50 6.7 – 8.7 [46,63]
RO5166017 Small molecule or natural product Hs Full agonist 7.3 pEC50 49
⤷ pEC50 7.3 (EC50 5.5x10-8 M) [49]
ralmitaront Small molecule or natural product Ligand has a PDB structure Hs Agonist 7.2 pEC50 19
⤷ pEC50 7.2 (EC50 5.85x10-8 M) [19]
tyramine Small molecule or natural product Ligand is endogenous in the given species Ligand has a PDB structure Rn Full agonist 6.9 – 7.2 pEC50 7-8,46
⤷ pEC50 6.9 – 7.2 [7-8,46]
β-phenylethylamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Mm Full agonist 6.3 – 7.4 pEC50 23,46,63
⤷ pEC50 6.3 – 7.4 [23,46,63]
3-iodothyronamine Small molecule or natural product Ligand is endogenous in the given species Mm Full agonist 6.5 – 7.0 pEC50 22,52,60
⤷ pEC50 6.5 – 7.0 [22,52,60]
2-phenyl-propylamine Small molecule or natural product Hs Agonist 6.5 – 7.0 pEC50 61
⤷ pEC50 6.5 – 7.0 (EC50 3.25x10-7 – 1.04x10-7 M) [61]
tyramine Small molecule or natural product Ligand is endogenous in the given species Ligand has a PDB structure Mm Full agonist 6.2 – 7.1 pEC50 7,23,46,63
⤷ pEC50 6.2 – 7.1 [7,23,46,63]
β-phenylethylamine Small molecule or natural product Ligand is endogenous in the given species Hs Full agonist 6.2 – 7.0 pEC50 5-6,23-24,28,61
⤷ pEC50 6.2 – 7.0 [5-6,23-24,28,61]
R(-)amphetamine Small molecule or natural product Ligand has a PDB structure Rn Partial agonist 6.5 – 6.7 pEC50 8,46
⤷ pEC50 6.5 – 6.7 [8,46]
β-phenylethylamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Rn Full agonist 6.4 – 6.6 pEC50 8,46
⤷ pEC50 6.4 – 6.6 [8,46]
dexamfetamine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.0 – 6.9 pEC50 5,27
⤷ pEC50 6.0 – 6.9 [5,27]
R(-)amphetamine Small molecule or natural product Ligand has a PDB structure Hs Full agonist 6.2 – 6.6 pEC50 5,27
⤷ pEC50 6.6 [5]
pEC50 6.2 (EC50 6x10-7 M) [27]
R(-)amphetamine Small molecule or natural product Ligand has a PDB structure Mm Full agonist 5.3 – 7.2 pEC50 46,63
⤷ pEC50 5.3 – 7.2 [46,63]
dexamfetamine Small molecule or natural product Approved drug Ligand has a PDB structure Rn Full agonist 6.1 – 6.4 pEC50 8,46
⤷ pEC50 6.1 – 6.4 [8,46]
tyramine Small molecule or natural product Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 5.8 – 6.7 pEC50 5-7,23-24,61
⤷ pEC50 5.8 – 6.7 [5-7,23-24,61]
octopamine Small molecule or natural product Rn Full agonist 5.9 pEC50 8
⤷ pEC50 5.9 [8]
octopamine Small molecule or natural product Mm Full agonist 5.4 – 5.8 pEC50 23,63
⤷ pEC50 5.4 – 5.8 [23,63]
octopamine Small molecule or natural product Hs Full agonist 4.8 – 5.8 pEC50 5-6,23-24,61
⤷ pEC50 4.8 – 5.8 [5-6,23-24,61]
ractopamine Small molecule or natural product Mm Agonist 4.8 pEC50 34
⤷ pEC50 4.8 (EC50 1.6x10-5 M) [34]
Description: Measuring chloride conductance in oocytes coexpressing hCFTR and mTAAR1, as a as a sensor for intracellular cAMP modulation.
ulotaront Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 6.8 pIC50 12
⤷ pIC50 6.8 (IC50 1.4x10-7 M) [12]
RO5256390 Small molecule or natural product N/A Partial agonist - - 32
⤷ [32]
View species-specific agonist tables
Agonist Comments
There is a lack of specific agonists, which makes investigation of the TA1 receptor difficult outside of isolated expression systems. Species differences do exist, although a greater body of comparable literature is required to confirm these. Radiolabelled 3-iodothyronamine has been synthesised [39] but has not been fully characterised and is not yet commercially available.

There are two reports of selective TA1 partial agonists. (1) RO5203648. In HEK293 cells, Ki values were 6.8nM (human TA1), 1nM (rat TA1) and 0.5nM (mouse TA1). EC50 (and Emax compared to β-Phenylethylamine) values in cAMP assay were 30nM (73%) for human, 6.8nM (59%) for rat and 4nM (48%) for mouse TA1 [50]. (2) RO5073012. Ki human TA1 6nM with 140 fold selectivity for TA1 over adrenergic α2. In functional assay EC50 (Emax) values were 23nM (35%) for human TA1, 25nM (24%) for rat TA1 and 23nM (26%) for mouse TA1 [20].

More recently described partial agonists from [18,51] with improved pharmacological profiles and pharmacokinetics compared to RO5166017. These are RO5256390 ((S)-4-((S)-2-phenyl-butyl)-4,5-dihydro-oxazol-2-ylamine) with Ki binding in HEK293 cells of 4nM (mouse TA1), 1nM (rat TA1) and 24nM (human TA1) and EC50 values in cAMP assays in HEK293 cells (Emax relative to β-phenylethylamine) of 2nM (79%) (mouse TA1); 5nM (107%) (rat TA1) and 16nM (98%) (human TA1 and RO5263397 ((S)-4-(3-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine with Ki of 1nM (mouse TA1), 9nM (rat TA1) and 4nM (human TA1) and EC50 (Emax relative to β-phenylethylamine) in cAMP assays in HEK293 cells of 1nM (59%) (mouse TA1), 47nM (76%) (rat TA1) and 17nM (81%) (human TA1).

Ractopamine's agonist activity at mTA1 is completely reversed by the antagonist EPPTB [34].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
EPPTB Small molecule or natural product Mm Inverse agonist 9.0 pKi 7,56
⤷ pKi 9.0 (Ki 9x10-10 M) [7,56]
EPPTB Small molecule or natural product Rn Inverse agonist 6.0 pKi 7
⤷ pKi 6.0 (Ki 9.42x10-7 M) [7]
EPPTB Small molecule or natural product Mm Inverse agonist 7.7 pIC50 7
⤷ pIC50 7.7 (IC50 1.9x10-8 M) [7]
EPPTB Small molecule or natural product Rn Inverse agonist 5.4 pIC50 7
⤷ pIC50 5.4 (IC50 4.5x10-6 M) [7]
EPPTB Small molecule or natural product Hs Inverse agonist 5.1 pIC50 7
⤷ pIC50 5.1 (IC50 7.487x10-6 M) [7]
View species-specific antagonist tables
Antagonist Comments
There are currently no commercially available antagonists available for the TA1 receptor, although lead compounds have been rationally synthesised but not yet fully characterised [59].

EPPTB (RO5212773) inhibited basal cAMP levels in HEK293 cells expressing human, rat and mouse TA1 receptors and has 1000 fold selectivity for the mouse TA1 receptor. EPPTB TA1 antagonism is not detected in Taar1 knockout mice [7]. In Schild analysis RO5212773 was a competitive antagonist [7].
Allosteric Modulator Comments
There are currently no known allosteric regulators of the TA1 receptor.
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family Adenylyl cyclase stimulation
Comments:  Tyramine causes an increase in intracellular cAMP in HEK293 or COS-7 cells expressing the TA1 receptor in vitro [6,8,29]. In addition, coupling to a promiscuous Gαq has been observed, resulting in increased intracellular calcium concentration [40]. In vivo transduction mechanisms have not yet been studied. In HEK293 cells expressing human, rat or mouse TA1 the receptor is reported to exhibit constitutive active as basal levels of cAMP were reduced by the TA1 selective compound RO5212773 (EPPTB) [7]. TA1 agonists (methamphetamine and β-PEA) increased intracellular cAMP levels in primary human astrocytes with TA1 knockdown significantly reducing intracellular cAMP levels in response to these agonists [10].
References:  6,8,29
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family
Comments:  RD-HGA16 cells express the promiscuous Gq protein Gα16 that allows the coupling of TA1 to the mobilisation of intracellular calcium [27-28].
References: 
Tissue Distribution Click here for help
Human pancreatic islet beta cells, duodenum and pylorus
Species:  Human
Technique:  immunohistochemistry
References:  45
CNS (region specific) & several peripheral tissues:
Stomach > amygdala, kidney, lung, small intestine > cerebellum, dorsal root ganglion, hippocampus, hypothalamus, liver, medulla oblongata, pancreas, pituitary gland, pontine reticular formation, prostate, skeletal muscle, spleen.
Species:  Human
Technique:  RT-PCR
References:  6
Circulating leukocytes of healthy subjects (upregulation occurs upon addition of phytohaemagglutinin).
Species:  Human
Technique:  RT-PCR
References:  11,41
Malignancy-derived B Cells
Species:  Human
Technique:  Western blot
References:  62
Leukocytes
Species:  Human
Technique:  RT-PCR
References:  4
Primary Tonsillar B Cells
Species:  Human
Technique:  Western blot
References:  13
Pancreatic islet β cells.
Species:  Human
Technique:  In situ hybridisation, RT-PCR
References:  47
Gastric D-Cells
Species:  Mouse
Technique:  RNA sequencing and RT-PCR
References:  2
Thyroid
Species:  Mouse
Technique:  Immunohistochemistry
References: 
Prefrontal cortical neurones
Species:  Mouse
Technique:  RT-PCR
References:  15
CNS:
Mitral cell layer of olfactory bulb, piriform cortex, arcuate, motor and mesencephalic trigeminal nuclei, lateral reticular and hypoglossal nuclei, cerebellar Purkinje cells, ventral horn of spinal cord > frontal, entorhinal and agranular cortices, ventral pallidum, thalamus, hypothalamic nuclei, hippocampus, ambiguus, dorsal raphe and gigantocellular reticular nuclei > septum, basal ganglia, amygdala, myelencephalon, dorsal horn of the spinal cord.
Species:  Mouse
Technique:  in situ hybridisation
References:  6
Substantia nigra (dopaminergic neurons).
Species:  Mouse
Technique:  Immunohistochemistry
References:  66
Brain regions associated with corticolimbic dopaminergic systems: substantia nigra/ventral tegmental area, nucleus accumbens, frontal cortex.
Species:  Mouse
Technique:  RT-PCR
References:  13
Thyroid
Species:  Rat
Technique:  Immunohistochemistry
References:  58
Cardiac ventricles.
Species:  Rat
Technique:  RT-PCR
References:  9
Aorta
Species:  Rat
Technique:  RT-PCR, Western blot
References:  17
Spinal neurones/motorneurones- adult and neonate
Species:  Rat
Technique:  PCR, in situ hybridisation, immunochemistry
References:  21
Tissue Distribution Comments
In the brain (mouse, rhesus monkey) the TA1 receptor localises to neurones within the monoaminergic pathways and there is emerging evidence for a modulatory role for TA1 on function of these systems. Co-expression of TA1 with the dopamine transporter (either within the same neurone or in adjacent neurones) implies direct/indirect modulation of CNS dopaminergic function. In cells expressing both human TA1 and a monoamine transporter (DAT, SERT or NET) signalling via TA1 is enhanced [38,64,66-67].
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Measurement of cAMP levels in HEK293 cells transfected with the human TA1 receptor.
Species:  Human
Tissue:  HEK293 cells.
Response measured:  Intracellular cAMP accumulation.
References:  29
Measurement of cAMP levels in HEK293 cells transfected with the murine TA1 receptor.
Species:  Mouse
Tissue:  HEK293 cells.
Response measured:  Intracellular cAMP accumulation.
References:  60,63
Measurement of cAMP levels in COS-7 cells transfected with the human TA1 receptor.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Intracellular cAMP accumulation.
References:  6
Measurement of the inward chloride current in Xenopus oocytes co-transfected with human TA1 and CFTR in response to tyramine.
Species:  Human
Tissue:  Xenopus laevis oocytes
Response measured:  Inward chloride current
References:  6
Fluorometry of intracellular calcium concentration in Chinese Hamster Ovary (CHO) cells expressing the promiscuous Gq, Gα16 and human TA1 receptor.
Species:  Human
Tissue:  CHO cells
Response measured:  Increase in cytopasmic calcium
References:  40
β-Lactamase reporter assay
Species:  Human
Tissue:  HEK293/Cre-bla cells
Response measured:  Elevated β-lactamase activity
References:  23
Measurement of cAMP levels in HEK293 cells transfected with the rat TA1 receptor.
Species:  Rat
Tissue:  HEK293 cells
Response measured:  Intracellular cAMP accumulation
References:  60
Mobilization of internal calcium in RD-HGA16cells transfected with unmodified human TA1
Species:  Human
Tissue:  RD-HGA16 cells
Response measured:  Mobilization of intracellular calcium
References:  27-28
Inhibition of firing frequency of dopamine neurones in slice preparation of mouse brain ventral tegmental area.
Species:  Mouse
Tissue:  Midbrain slice
Response measured:  Inhibition of spontaneous dopamine neurone firing frequency
References:  7
β-Lactamase reporter assay
Species:  Mouse
Tissue:  HEK293/Cre-bla cells
Response measured:  Elevated β-lactamase activity
References:  23
Activation of leukocytes
Species:  Human
Tissue:  PMN, T and B cells
Response measured:  Chemotactic migration towards TA1 ligands (β-Phenylethylamine, tyramine and 3-iodothyronamine), trace amine induced IL-4 secretion (T-cells) and trace amine induced regulation of T cell marker RNA expression, trace amine induced IgE secretion in B cells.
References:  4
Measurement of cAMP levels in human cultured astrocytes.
Species:  Human
Tissue:  Astrocytes
Response measured:  cAMP accumulation
References:  10
Increase in glucose-dependent insulin secretion
Species:  Rat
Tissue:  INS1E cells
Response measured:  Potentiation of glucose-induced insulin secretion
References:  45
Functional Assay Comments
Expression systems have proved effective in establishing assays for TA1 activity without the need for specific agonists and antagonists.
Physiological Functions Click here for help
β-PEA inhibited uptake and induced efflux of [3H]dopamine and [3H]serotonin in striatal and [3H]norepinephrine in thalamic synaptosomes of wild-type mice and in HEK293 cells expressing TA1.
Species:  Mouse
Tissue:  Striatal and thalamic synaptosomes.
References:  64,67
Inhibition of firing frequency of dopminergic neurones
Species:  Mouse
Tissue:  Brain
References:  7,30,49-50
RO5166017 and RO5263397 inhibited expression of cocaine memory. Repeated administration of RO5166017 showed continually inhibitory effect on expression of cocaine reward memory but no no effect on reconsolidation, extinction, or storage of cocaine reward memory.
Species:  Rat
Tissue:  in vivo whole animal
References:  33
Improvement in glucose tolerance following an oral glucose tolerance test and reduction in body weight in wild type and diabetic db/db mice in response to TAAR1 agonist RO5166017.
Species:  Mouse
Tissue:  in vivo whole animal
References:  45
The selectve Taar1 agonists RO5203648 (partial agonist) and RO5256390 (full agonist) reduced reinforcing and rewarding properties of cocaine.
Species:  Rat
Tissue:  in vivo whole animal
References:  43
Physiological Consequences of Altering Gene Expression Click here for help
Mice deficient in the TA1 receptor possess a phenotype with minor spontaneous hyperactivity, reduced prepulse inhibition, increased sensitisation to the psychomotor-stimulating effects of amphetamine, raised levels of dopamine and noradrenaline in the dorsal striatum, increased striatal D2 receptor expression and an elevated spontaneous firing rate of dopaminergic neurons in the ventral tegmental area compared with the wild type. This has been proposed as an animal model of schizophrenia and also as hemi-parkinsonian.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells
References:  30,55,63
β-PEA inhibited uptake and induced efflux of [3H]dopamine and [3H]serotonin in striatal and [3H]norepinephrine in thalamic synaptosomes of wild-type but not TA1 knockout mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  64,67
Knockout animals exhibit a significant augmentation of methamphetamine induced locomotor activity and conditioned placement preference.
Species:  Mouse
Tissue:  in vivo whole animal
Technique:  Targeting in embryonic stem cells
References:  1
Functional interaction between TA1 and Dopamine D2 receptor. In TA1 knockout mouse haloperidol -induced striatal c-Fos expression and catalepsy are reduced.
Species:  Mouse
Tissue:  in vivo whole animal
Technique:  Targeting in embryonic stem cells
References:  16
Auto-inhibition of MDMA (Ecstasy) responses by TA1 receptor. Knockout animals indicate a role for TA1 in MDMA mediated hypothermia and in auto-inhibition of MDMA responses including release of dopamine and 5-HT in dorsal striatum and nucleus accumbens, locomotor activity, striatal tyrosine hydrolxylase phsophorylation.
Species:  Mouse
Tissue:  in vivo whole animal
Technique:  Targeting in embryonic stem cells
References:  13
Brain-specific overexpression of TA1 alters monoaminergic neurotransmission and decreased sensitivty to amphetamine. Increased spontaneous firing activity of monaminergic neurones in ventral tegmental area, dorsal raphe nucleus and locus coeruleus resulting from reduced GABAergic inhibitory input. Elevated basal release of monoamines. Hyposensitivity to locomotor effects of amphetamine that could be reversed with the TA1 partial agonist RO5073012.
Species:  Mouse
Tissue:  in vivo whole animal
Technique:  Gene over expression
References:  48
Basal and stimulated dopamine (DA) release was higher in the nucleus accumbens of TA1-KO mice in vivo and ex vivo but DAT function remained unaltered. The TA1 agonist RO5166017 had no effect on DA release from the nucleus accumbens in brain slices from TA1-KO mice but decreased evoked DA release in tissue from WT animals that was prevented by the TA1 antagonist EPPTB. The D2 agonist quinpirole decreased DA release in both WT and KO brain slices and this decrease was augmented in the presence of RO5166017 in the WT but not KO tissues, suggesting close interaction between TA1 and D2 autoreceptor regulation of dopamine release in the mouse nucleus accumbens that was confirmed by a paired pulse experiment.
Species:  Mouse
Tissue:  in vivo whole animal and in vitro brain slices
Technique:  Targeting in embryonic stem cells
References:  26
TA1 KO mice showed greater preference for/consumption of ethanol, more sedation and less locomotor activity in response to acute ethanol than wild type animals.
Species:  Mouse
Tissue:  in vivo whole animal
Technique:  Gene targeting in embryonic stem cells
References:  35
Climbing and some stereotypies elicited by high dose apomorphine (2-5mg kg-1) were decreased in the TA1 KO mouse compared to wild type.
Species:  Mouse
Tissue:  in vivo whole animal
Technique:  Gene targeting in embryonic stem cells
References:  57
Mice deficient in TA1 receptor lack the the glucose lowering and food consumption reduction response to RO5166017 observed in wild type animals.
Species:  Mouse
Tissue:  in vivo whole animal
Technique:  Gene targeting in embryonic stem cells
References:  45
TA1 knockout mice exhibited less severe dopaminergic neurodegeneration following intrastriatal administration of 6-hydroxydopamine than wild type controls. Following medial forebrain bundle administration of 6-hydroxydopamine and subsequent L-DOPA treatment, TA1 KO mice exhibited more pronounced rotational behaviour and dyskinesia but this could be counteracted by RO5166017.
Species:  Mouse
Tissue:  in vivo whole animal and brain
Technique:  Gene targeting in embryonic stem cells
References:  3
D2, but not D1, dopamine receptors were over-expressed at mRNA and protein levels, in the striatum of TA1 KO mice and exhibited pronounced supersensitivity.
Species:  Mouse
Tissue:  in vivo whole animal and striatum
Technique:  Gene targeting in embryonic stem cells
References:  14
TA1 KO mice show altered subunit composition and reduced functionality of NMDA receptors resulting in dysregulated cortical glutaminergic transmission and aberrant behavoiurs consistent with a perseverative and impulsive phenotype.
Species:  None
Tissue:  in vivo whole animal and brain
Technique:  Gene targeting in embryonic stem cells
References:  15
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Taar1tm1Tdw Taar1tm1Tdw/Taar1tm1Tdw
involves: 129S1/Sv * C57BL/6J		 MGI:2148258  MP:0003964 abnormal noradrenaline level PMID: 17212650 
Taar1tm1Tdw Taar1tm1Tdw/Taar1tm1Tdw
involves: 129S1/Sv * C57BL/6J		 MGI:2148258  MP:0003088 abnormal prepulse inhibition PMID: 17212650 
Taar1tm1Tdw Taar1tm1Tdw/Taar1tm1Tdw
involves: 129S1/Sv * C57BL/6J		 MGI:2148258  MP:0009749 enhanced behavioral response to addictive substance PMID: 17212650 
Taar1tm1Tdw Taar1tm1Tdw/Taar1tm1Tdw
involves: 129S1/Sv * C57BL/6J		 MGI:2148258  MP:0001906 increased dopamine level PMID: 17212650 
Taar1tm1Tdw Taar1tm1Tdw/Taar1tm1Tdw
involves: 129S1/Sv * C57BL/6J		 MGI:2148258  MP:0008873 increased physiological sensitivity to xenobiotic PMID: 17212650 
Biologically Significant Variant Comments
A SNP (rs8192619) in the TA1 receptor was reported in a large candidate gene association study investigating genetic risk factors that may contribute to the aetiology of fibromyalgia [53].
General Comments
For comprehensive reviews of the TA1 receptor see: [25,36-37,42,44,54,65].

References

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1. Achat-Mendes C, Lynch LJ, Sullivan KA, Vallender EJ, Miller GM. (2012) Augmentation of methamphetamine-induced behaviors in transgenic mice lacking the trace amine-associated receptor 1. Pharmacol Biochem Behav, 101 (2): 201-7. [PMID:22079347]

2. Adriaenssens A, Lam BY, Billing L, Skeffington K, Sewing S, Reimann F, Gribble F. (2015) A Transcriptome-Led Exploration of Molecular Mechanisms Regulating Somatostatin-Producing D-Cells in the Gastric Epithelium. Endocrinology, 156 (11): 3924-36. [PMID:26241122]

3. Alvarsson A, Zhang X, Stan TL, Schintu N, Kadkhodaei B, Millan MJ, Perlmann T, Svenningsson P. (2015) Modulation by Trace Amine-Associated Receptor 1 of Experimental Parkinsonism, L-DOPA Responsivity, and Glutamatergic Neurotransmission. J Neurosci, 35 (41): 14057-69. [PMID:26468205]

4. Babusyte A, Kotthoff M, Fiedler J, Krautwurst D. (2013) Biogenic amines activate blood leukocytes via trace amine-associated receptors TAAR1 and TAAR2. J Leukoc Biol, 93 (3): 387-94. [PMID:23315425]

5. Barak LS, Salahpour A, Zhang X, Masri B, Sotnikova TD, Ramsey AJ, Violin JD, Lefkowitz RJ, Caron MG, Gainetdinov RR. (2008) Pharmacological characterization of membrane-expressed human trace amine-associated receptor 1 (TAAR1) by a bioluminescence resonance energy transfer cAMP biosensor. Mol Pharmacol, 74 (3): 585-594. [PMID:18524885]

6. Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, Durkin MM, Lakhlani PP, Bonini JA, Pathirana S et al.. (2001) Trace amines: identification of a family of mammalian G protein-coupled receptors. Proc Natl Acad Sci USA, 98 (16): 8966-71. [PMID:11459929]

7. Bradaia A, Trube G, Stalder H, Norcross RD, Ozmen L, Wettstein JG, Pinard A, Buchy D, Gassmann M, Hoener MC et al.. (2009) The selective antagonist EPPTB reveals TAAR1-mediated regulatory mechanisms in dopaminergic neurons of the mesolimbic system. Proc Natl Acad Sci USA, 106 (47): 20081-6. [PMID:19892733]

8. Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, Darland T, Suchland KL, Pasumamula S, Kennedy JL et al.. (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. [PMID:11723224]

9. Chiellini G, Frascarelli S, Ghelardoni S, Carnicelli V, Tobias SC, DeBarber A, Brogioni S, Ronca-Testoni S, Cerbai E, Grandy DK et al.. (2007) Cardiac effects of 3-iodothyronamine: a new aminergic system modulating cardiac function. FASEB J, 21 (7): 1597-608. [PMID:17284482]

10. Cisneros IE, Ghorpade A. (2014) Methamphetamine and HIV-1-induced neurotoxicity: role of trace amine associated receptor 1 cAMP signaling in astrocytes. Neuropharmacology, 85: 499-507. [PMID:24950453]

11. D'Andrea G, Terrazzino S, Fortin D, Farruggio A, Rinaldi L, Leon A. (2003) HPLC electrochemical detection of trace amines in human plasma and platelets and expression of mRNA transcripts of trace amine receptors in circulating leukocytes. Neurosci Lett, 346 (1-2): 89-92. [PMID:12850555]

12. Dedic N, Jones PG, Hopkins SC, Lew R, Shao L, Campbell JE, Spear KL, Large TH, Campbell UC, Hanania T et al.. (2019) SEP-363856, a Novel Psychotropic Agent with a Unique, Non-D2 Receptor Mechanism of Action. J Pharmacol Exp Ther, 371 (1): 1-14. [PMID:31371483]

13. Di Cara B, Maggio R, Aloisi G, Rivet JM, Lundius EG, Yoshitake T, Svenningsson P, Brocco M, Gobert A, De Groote L et al.. (2011) Genetic deletion of trace amine 1 receptors reveals their role in auto-inhibiting the actions of ecstasy (MDMA). J Neurosci, 31 (47): 16928-40. [PMID:22114263]

14. Espinoza S, Ghisi V, Emanuele M, Leo D, Sukhanov I, Sotnikova TD, Chieregatti E, Gainetdinov RR. (2015) Postsynaptic D2 dopamine receptor supersensitivity in the striatum of mice lacking TAAR1. Neuropharmacology, 93: 308-13. [PMID:25721394]

15. Espinoza S, Lignani G, Caffino L, Maggi S, Sukhanov I, Leo D, Mus L, Emanuele M, Ronzitti G, Harmeier A et al.. (2015) TAAR1 Modulates Cortical Glutamate NMDA Receptor Function. Neuropsychopharmacology, 40 (9): 2217-27. [PMID:25749299]

16. Espinoza S, Salahpour A, Masri B, Sotnikova TD, Messa M, Barak LS, Caron MG, Gainetdinov RR. (2011) Functional interaction between trace amine-associated receptor 1 and dopamine D2 receptor. Mol Pharmacol, 80 (3): 416-25. [PMID:21670104]

17. Fehler M, Broadley KJ, Ford WR, Kidd EJ. (2010) Identification of trace-amine-associated receptors (TAAR) in the rat aorta and their role in vasoconstriction by β-phenylethylamine. Naunyn Schmiedebergs Arch Pharmacol, 382 (4): 385-98. [PMID:20809238]

18. Galley G, Beurier A, Décoret G, Goergler A, Hutter R, Mohr S, Pähler A, Schmid P, Türck D, Unger R et al.. (2016) Discovery and Characterization of 2-Aminooxazolines as Highly Potent, Selective, and Orally Active TAAR1 Agonists. ACS Med Chem Lett, 7 (2): 192-7. [PMID:26985297]

19. Galley G, Hoener M, Norcross R, Pflieger P. (2017) 5-ethyl-4-methyl-pyrazole-3-carboxamide derivative having activity as agonist of taar. Patent number: WO2017157873A1. Assignee: Hoffmann-La Roche. Priority date: 17/03/2016. Publication date: 21/09/2017.

20. Galley G, Stalder H, Goergler A, Hoener MC, Norcross RD. (2012) Optimisation of imidazole compounds as selective TAAR1 agonists: discovery of RO5073012. Bioorg Med Chem Lett, 22 (16): 5244-8. [PMID:22795332]

21. Gozal EA, O'Neill BE, Sawchuk MA, Zhu H, Halder M, Chou CC, Hochman S. (2014) Anatomical and functional evidence for trace amines as unique modulators of locomotor function in the mammalian spinal cord. Front Neural Circuits, 8: 134. [PMID:25426030]

22. 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. [PMID:16451074]

23. Hu LA, Zhou T, Ahn J, Wang S, Zhou J, Hu Y, Liu Q. (2009) Human and mouse trace amine-associated receptor 1 have distinct pharmacology towards endogenous monoamines and imidazoline receptor ligands. Biochem J, 424 (1): 39-45. [PMID:19725810]

24. Kleinau G, Pratzka J, Nürnberg D, Grüters A, Führer-Sakel D, Krude H, Köhrle J, Schöneberg T, Biebermann H. (2011) Differential modulation of Beta-adrenergic receptor signaling by trace amine-associated receptor 1 agonists. PLoS ONE, 6 (10): e27073. [PMID:22073124]

25. Lam VM, Espinoza S, Gerasimov AS, Gainetdinov RR, Salahpour A. (2015) In-vivo pharmacology of Trace-Amine Associated Receptor 1. Eur J Pharmacol, 763 (Pt B): 136-42. [PMID:26093041]

26. Leo D, Mus L, Espinoza S, Hoener MC, Sotnikova TD, Gainetdinov RR. (2014) Taar1-mediated modulation of presynaptic dopaminergic neurotransmission: role of D2 dopamine autoreceptors. Neuropharmacology, 81: 283-91. [PMID:24565640]

27. Lewin AH, Miller GM, Gilmour B. (2011) Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class. Bioorg Med Chem, 19 (23): 7044-8. [PMID:22037049]

28. Lewin AH, Navarro HA, Mascarella SW. (2008) Structure-activity correlations for beta-phenethylamines at human trace amine receptor 1. Bioorg Med Chem, 16 (15): 7415-23. [PMID:18602830]

29. Lindemann L, Ebeling M, Kratochwil NA, Bunzow JR, Grandy DK, Hoener MC. (2005) Trace amine-associated receptors form structurally and functionally distinct subfamilies of novel G protein-coupled receptors. Genomics, 85 (3): 372-85. [PMID:15718104]

30. Lindemann L, Meyer CA, Jeanneau K, Bradaia A, Ozmen L, Bluethmann H, Bettler B, Wettstein JG, Borroni E, Moreau JL et al.. (2008) Trace amine-associated receptor 1 modulates dopaminergic activity. J Pharmacol Exp Ther, 324 (3): 948-56. [PMID:18083911]

31. Liu H, Zheng Y, Wang Y, Wang Y, He X, Xu P, Huang S, Yuan Q, Zhang X, Wang L et al.. (2023) Recognition of methamphetamine and other amines by trace amine receptor TAAR1. Nature, 624 (7992): 663-671. [PMID:37935377]

32. Liu J, Johnson B, Wu R, Seaman Jr R, Vu J, Zhu Q, Zhang Y, Li JX. (2020) TAAR1 agonists attenuate extended-access cocaine self-administration and yohimbine-induced reinstatement of cocaine-seeking. Br J Pharmacol, 177 (15): 3403-3414. [PMID:32246467]

33. Liu JF, Thorn DA, Zhang Y, Li JX. (2016) Effects of Trace Amine-associated Receptor 1 Agonists on the Expression, Reconsolidation, and Extinction of Cocaine Reward Memory. Int J Neuropsychopharmacol, 19 (7). [PMID:26822713]

34. Liu X, Grandy DK, Janowsky A. (2014) Ractopamine, a livestock feed additive, is a full agonist at trace amine-associated receptor 1. J Pharmacol Exp Ther, 350 (1): 124-9. [PMID:24799633]

35. Lynch LJ, Sullivan KA, Vallender EJ, Rowlett JK, Platt DM, Miller GM. (2013) Trace amine associated receptor 1 modulates behavioral effects of ethanol. Subst Abuse, 7: 117-26. [PMID:23861588]

36. Maguire JJ, Parker WA, Foord SM, Bonner TI, Neubig RR, Davenport AP. (2009) International Union of Pharmacology. LXXII. Recommendations for trace amine receptor nomenclature. Pharmacol Rev, 61 (1): 1-8. [PMID:19325074]

37. Miller GM. (2011) The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity. J Neurochem, 116 (2): 164-76. [PMID:21073468]

38. Miller GM, Verrico CD, Jassen A, Konar M, Yang H, Panas H, Bahn M, Johnson R, Madras BK. (2005) Primate trace amine receptor 1 modulation by the dopamine transporter. J Pharmacol Exp Ther, 313 (3): 983-94. [PMID:15764732]

39. Miyakawa M, Scanlan TS. (2006) Synthesis of [125I]-, [2H]-, and [3H]-labelled 3-iodothyronamine (T1AM). Synthetic Communications, 36: 891-902.

40. Navarro HA, Gilmour BP, Lewin AH. (2006) A rapid functional assay for the human trace amine-associated receptor 1 based on the mobilization of internal calcium. J Biomol Screen, 11 (6): 688-93. [PMID:16831861]

41. Nelson DA, Tolbert MD, Singh SJ, Bost KL. (2007) Expression of neuronal trace amine-associated receptor (Taar) mRNAs in leukocytes. J Neuroimmunol, 192 (1-2): 21-30. [PMID:17900709]

42. Pei Y, Asif-Malik A, Canales JJ. (2016) Trace Amines and the Trace Amine-Associated Receptor 1: Pharmacology, Neurochemistry, and Clinical Implications. Front Neurosci, 10: 148. [PMID:27092049]

43. Pei Y, Mortas P, Hoener MC, Canales JJ. (2015) Selective activation of the trace amine-associated receptor 1 decreases cocaine's reinforcing efficacy and prevents cocaine-induced changes in brain reward thresholds. Prog Neuropsychopharmacol Biol Psychiatry, 63: 70-5. [PMID:26048337]

44. Piehl S, Hoefig CS, Scanlan TS, Köhrle J. (2011) Thyronamines--past, present, and future. Endocr Rev, 32 (1): 64-80. [PMID:20880963]

45. Raab S, Wang H, Uhles S, Cole N, Alvarez-Sanchez R, Künnecke B, Ullmer C, Matile H, Bedoucha M, Norcross RD et al.. (2016) Incretin-like effects of small molecule trace amine-associated receptor 1 agonists. Mol Metab, 5 (1): 47-56. [PMID:26844206]

46. Reese EA, Bunzow JR, Arttamangkul S, Sonders MS, Grandy DK. (2007) Trace amine-associated receptor 1 displays species-dependent stereoselectivity for isomers of methamphetamine, amphetamine, and para-hydroxyamphetamine. J Pharmacol Exp Ther, 321 (1): 178-86. [PMID:17218486]

47. Regard JB, Kataoka H, Cano DA, Camerer E, Yin L, Zheng YW, Scanlan TS, Hebrok M, Coughlin SR. (2007) Probing cell type-specific functions of Gi in vivo identifies GPCR regulators of insulin secretion. J Clin Invest, 117 (12): 4034-43. [PMID:17992256]

48. Revel FG, Meyer CA, Bradaia A, Jeanneau K, Calcagno E, André CB, Haenggi M, Miss MT, Galley G, Norcross RD et al.. (2012) Brain-specific overexpression of trace amine-associated receptor 1 alters monoaminergic neurotransmission and decreases sensitivity to amphetamine. Neuropsychopharmacology, 37 (12): 2580-92. [PMID:22763617]

49. Revel FG, Moreau JL, Gainetdinov RR, Bradaia A, Sotnikova TD, Mory R, Durkin S, Zbinden KG, Norcross R, Meyer CA et al.. (2011) TAAR1 activation modulates monoaminergic neurotransmission, preventing hyperdopaminergic and hypoglutamatergic activity. Proc Natl Acad Sci USA, 108 (20): 8485-90. [PMID:21525407]

50. Revel FG, Moreau JL, Gainetdinov RR, Ferragud A, Velázquez-Sánchez C, Sotnikova TD, Morairty SR, Harmeier A, Groebke Zbinden K, Norcross RD et al.. (2012) Trace amine-associated receptor 1 partial agonism reveals novel paradigm for neuropsychiatric therapeutics. Biol Psychiatry, 72 (11): 934-42. [PMID:22705041]

51. Revel FG, Moreau JL, Pouzet B, Mory R, Bradaia A, Buchy D, Metzler V, Chaboz S, Groebke Zbinden K, Galley G et al.. (2013) A new perspective for schizophrenia: TAAR1 agonists reveal antipsychotic- and antidepressant-like activity, improve cognition and control body weight. Mol Psychiatry, 18 (5): 543-56. [PMID:22641180]

52. Scanlan TS, Suchland KL, Hart ME, Chiellini G, Huang Y, Kruzich PJ, Frascarelli S, Crossley DA, Bunzow JR, Ronca-Testoni S et al.. (2004) 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone. Nat Med, 10 (6): 638-42. [PMID:15146179]

53. Smith SB, Maixner DW, Fillingim RB, Slade G, Gracely RH, Ambrose K, Zaykin DV, Hyde C, John S, Tan K et al.. (2012) Large candidate gene association study reveals genetic risk factors and therapeutic targets for fibromyalgia. Arthritis Rheum, 64 (2): 584-93. [PMID:21905019]

54. Sotnikova TD, Caron MG, Gainetdinov RR. (2009) Trace amine-associated receptors as emerging therapeutic targets. Mol Pharmacol, 76 (2): 229-35. [PMID:19389919]

55. Sotnikova TD, Zorina OI, Ghisi V, Caron MG, Gainetdinov RR. (2008) Trace amine associated receptor 1 and movement control. Parkinsonism Relat Disord, 14 Suppl 2: S99-102. [PMID:18585080]

56. Stalder H, Hoener MC, Norcross RD. (2011) Selective antagonists of mouse trace amine-associated receptor 1 (mTAAR1): discovery of EPPTB (RO5212773). Bioorg Med Chem Lett, 21 (4): 1227-31. [PMID:21237643]

57. Sukhanov I, Espinoza S, Yakovlev DS, Hoener MC, Sotnikova TD, Gainetdinov RR. (2014) TAAR1-dependent effects of apomorphine in mice. Int J Neuropsychopharmacol, 17 (10): 1683-93. [PMID:24925023]

58. Szumska J, Qatato M, Rehders M, Führer D, Biebermann H, Grandy DK, Köhrle J, Brix K. (2015) Trace Amine-Associated Receptor 1 Localization at the Apical Plasma Membrane Domain of Fisher Rat Thyroid Epithelial Cells Is Confined to Cilia. Eur Thyroid J, 4 (Suppl 1): 30-41. [PMID:26601071]

59. Tan ES, Groban ES, Jacobson MP, Scanlan TS. (2008) Toward deciphering the code to aminergic G protein-coupled receptor drug design. Chem Biol, 15 (4): 343-53. [PMID:18420141]

60. Tan ES, Miyakawa M, Bunzow JR, Grandy DK, Scanlan TS. (2007) Exploring the structure-activity relationship of the ethylamine portion of 3-iodothyronamine for rat and mouse trace amine-associated receptor 1. J Med Chem, 50 (12): 2787-98. [PMID:17497842]

61. Wainscott DB, Little SP, Yin T, Tu Y, Rocco VP, He JX, Nelson DL. (2007) Pharmacologic characterization of the cloned human trace amine-associated receptor1 (TAAR1) and evidence for species differences with the rat TAAR1. J Pharmacol Exp Ther, 320 (1): 475-85. [PMID:17038507]

62. Wasik AM, Millan MJ, Scanlan T, Barnes NM, Gordon J. (2012) Evidence for functional trace amine associated receptor-1 in normal and malignant B cells. Leuk Res, 36 (2): 245-9. [PMID:22036195]

63. Wolinsky TD, Swanson CJ, Smith KE, Zhong H, Borowsky B, Seeman P, Branchek T, Gerald CP. (2007) The Trace Amine 1 receptor knockout mouse: an animal model with relevance to schizophrenia. Genes Brain Behav, 6 (7): 628-39. [PMID:17212650]

64. Xie Z, Miller GM. (2008) Beta-phenylethylamine alters monoamine transporter function via trace amine-associated receptor 1: implication for modulatory roles of trace amines in brain. J Pharmacol Exp Ther, 325 (2): 617-28. [PMID:18182557]

65. Xie Z, Miller GM. (2009) Trace amine-associated receptor 1 as a monoaminergic modulator in brain. Biochem Pharmacol, 78 (9): 1095-104. [PMID:19482011]

66. Xie Z, Westmoreland SV, Bahn ME, Chen GL, Yang H, Vallender EJ, Yao WD, Madras BK, Miller GM. (2007) Rhesus monkey trace amine-associated receptor 1 signaling: enhancement by monoamine transporters and attenuation by the D2 autoreceptor in vitro. J Pharmacol Exp Ther, 321 (1): 116-27. [PMID:17234900]

67. Xie Z, Westmoreland SV, Miller GM. (2008) Modulation of monoamine transporters by common biogenic amines via trace amine-associated receptor 1 and monoamine autoreceptors in human embryonic kidney 293 cells and brain synaptosomes. J Pharmacol Exp Ther, 325 (2): 629-40. [PMID:18310473]

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