Affinage

TAAR1

Trace amine-associated receptor 1 · UniProt Q96RJ0

Length
339 aa
Mass
39.1 kDa
Annotated
2026-06-10
100 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TAAR1 is a Gαs-coupled G-protein-coupled receptor that senses endogenous trace amines (β-phenylethylamine, tyramine, 3-iodothyronamine) and amphetamines, transducing these signals into cAMP elevation as its primary output (PMID:17038507, PMID:18524885). Unusually for a GPCR, native TAAR1 is largely retained intracellularly, and forcing surface expression by adding an N-terminal glycosylation site enables its pharmacological characterization (PMID:18524885); in dopamine neurons it functions as an obligate intracellular receptor that couples to two distinct Gα subunits in separate compartments—Gα13 near the endoplasmic reticulum to activate RhoA, and GαS throughout the cell to drive PKA/cAMP, both abolished in knockout cells and restored by compartment-targeted Gα peptide inhibitors (PMID:31399635). In the brain, TAAR1 acts as a tonic brake on monoaminergic tone: it activates inwardly rectifying K+ (GIRK) channels to suppress basal firing of VTA dopamine and dorsal raphe serotonin neurons (PMID:19892733, PMID:21525407), potentiates D2 autoreceptor-mediated presynaptic dopamine inhibition (PMID:24565640), and forms a functional heteromer with the dopamine D2L receptor that biases TAAR1 toward β-arrestin-2 signaling and dampens GSK3β activation (PMID:26372541). Loss of TAAR1 produces D2 receptor supersensitivity with dysregulated AKT/GSK3β signaling (PMID:25721394) and altered NMDA receptor subunit composition in prefrontal cortex linked to impulsive behavior (PMID:25749299). TAAR1 also tunes dopamine synthesis by promoting CaMKII/PKA-dependent phosphorylation of tyrosine hydroxylase (PMID:29545750). CRISPR rescue of a non-functional Taar1 allele establishes a causal role in methamphetamine intake and thermal responses (PMID:31274109). Cryo-EM structures define a rigid primary-amine recognition pocket anchored by the conserved acidic residue D3.32, a twin toggle-switch activation mechanism, and a second binding pocket that governs Gs-versus-Gq signaling bias and ligand polypharmacology (PMID:37963465, PMID:37935377, PMID:37935376). Beyond the CNS, TAAR1 signals through Gαs in pancreatic β-cells to drive insulin secretion and proliferation (PMID:30670596), in leukocytes to mediate amine- and methamphetamine-driven immune responses (PMID:23315425, PMID:26302754), and in thyroid epithelium where it is required for normal thyroglobulin processing (PMID:29615904).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2006 Medium

    Established that human TAAR1 is a functional Gαs-coupled receptor for trace amines, defining its core signaling output and distinguishing it pharmacologically from classical monoamine receptors.

    Evidence Stable expression of HA-tagged human TAAR1 with Gαs in cells, cAMP accumulation assay with β-phenylethylamine and trace amines

    PMID:17038507

    Open questions at the time
    • No genetic KO validation of trace-amine specificity in this study
    • Endogenous physiological agonist not resolved
    • Subcellular site of signaling not addressed
  2. 2008 High

    Explained why TAAR1 is pharmacologically difficult to study by showing it is normally intracellularly retained, and that engineered surface expression permits agonist-driven cAMP signaling.

    Evidence N-terminal glycosylation-tag engineering, stable cell lines, BRET cAMP/EPAC biosensor

    PMID:18524885

    Open questions at the time
    • Did not establish whether intracellular retention reflects native function
    • Mechanism of retention not defined
  3. 2009 High

    Defined TAAR1's first cellular effector mechanism in vivo—activation of Kir channels to tonically suppress VTA dopamine neuron firing—and mapped species-specific ligand selectivity to specific transmembrane residues.

    Evidence EPPTB antagonist pharmacology and patch-clamp in brain slices with KO validation; site-directed mutagenesis of TM4/TM7 residues with cAMP assays

    PMID:19256523 PMID:19892733

    Open questions at the time
    • G-protein/channel coupling intermediary not resolved
    • Endogenous agonist driving tonic activation not identified
  4. 2011 High

    Extended TAAR1's modulatory role to serotonergic neurons and revealed cross-talk with 5-HT1A receptors, establishing anatomical specificity tied to TAAR1 expression.

    Evidence Selective agonist RO5166017, brain-slice electrophysiology, WT vs KO comparison, behavioral pharmacology

    PMID:21525407

    Open questions at the time
    • Molecular basis of TAAR1/5-HT1A cross-talk not defined
    • Whether interaction is heteromeric or downstream unresolved
  5. 2014 High

    Showed TAAR1 modulates presynaptic dopamine release by potentiating D2 autoreceptor function and supporting D2 short-term plasticity, refining its role in dopaminergic feedback.

    Evidence Fast-scan cyclic voltammetry, microdialysis, agonist/antagonist pharmacology, TAAR1-KO mice

    PMID:24565640

    Open questions at the time
    • Direct physical TAAR1-D2 interaction not tested here
    • No effect on DAT clearance
  6. 2015 High

    Identified TAAR1-D2L heteromerization as a molecular mechanism switching TAAR1 signaling from Gαs/cAMP toward β-arrestin-2 and reducing GSK3β activation, and showed TAAR1 loss causes D2 supersensitivity and altered NMDA/glutamate signaling.

    Evidence Reciprocal co-IP in cells and brain tissue, β-arrestin-2 and cAMP assays, KO and overexpressing rats; KO mouse molecular/behavioral profiling of D2, AKT/GSK3β, and NMDA subunits

    PMID:25721394 PMID:25749299 PMID:26372541 PMID:26640076

    Open questions at the time
    • Stoichiometry and structural interface of the heteromer not defined
    • Causal chain from heteromer to behavior not fully dissected
  7. 2018 High

    Linked TAAR1 to dopamine biosynthesis by showing T1AM-activated TAAR1 phosphorylates tyrosine hydroxylase via CaMKII (Ser19) and PKA (Ser40), while distinguishing TAAR1-independent effects of other trace amines.

    Evidence TH phosphorylation Western blots, amperometry, kinase inhibitors, TAAR1-KO mice, EPPTB

    PMID:29545750

    Open questions at the time
    • Quantitative contribution to dopamine output in vivo unclear
    • Why tyramine/β-PEA act TAAR1-independently not explained
  8. 2019 High

    Revealed TAAR1 as an obligate intracellular receptor that signals from two subcellular pools via distinct Gα subunits (Gα13/RhoA at the ER and GαS/PKA cell-wide), reframing how amphetamine engages TAAR1.

    Evidence Compartment-targeted RhoA-FRET and PKA-FRET sensors, KO cells/mice, cell-permeable Gα-inhibitory peptides

    PMID:31399635

    Open questions at the time
    • How extracellular amphetamine reaches intracellular receptor not fully resolved
    • Functional consequences of RhoA arm in behavior unclear
  9. 2019 High

    Established causality for TAAR1 in methamphetamine intake and thermal response via CRISPR rescue, and identified genetic epistasis with the mu-opioid receptor.

    Evidence CRISPR-Cas9 correction of non-functional Taar1 in DBA/2J mice, interval mapping, epistasis analysis, behavior

    PMID:31274109

    Open questions at the time
    • Molecular basis of Taar1-Oprm1 epistasis not defined
    • Circuit mediating methamphetamine avoidance not mapped
  10. 2018 Medium

    Extended TAAR1 function to peripheral tissues, demonstrating a requirement for normal TSH-regulated thyroglobulin processing and identifying loss-of-function human variants relevant to metabolism.

    Evidence Taar1-KO mice with thyroid hormone, TSH-receptor localization, and cathepsin readouts; in vitro functional characterization of R23C and S49L variants

    PMID:29225575 PMID:29615904

    Open questions at the time
    • No rescue experiment for thyroid phenotype
    • Human variant phenotype not validated in vivo
    • Mechanism linking TAAR1 to cathepsin/cystatin network unknown
  11. 2020 Medium

    Showed TAAR1 mediates tyramine-driven negative feedback on glutamate release in the substantia nigra, integrating it into MAO-dependent amine homeostasis.

    Evidence TAAR1-KO mice, in vivo glutamate biosensor, mass spectrometry imaging of tyramine, localization mapping

    PMID:33579534

    Open questions at the time
    • Direct vs network-level mechanism on glutamate not resolved
    • Single lab
  12. 2023 High

    Determined the structural basis of TAAR1 ligand recognition and signaling bias, defining the D3.32-anchored primary amine pocket, a twin toggle activation switch, and a second binding pocket controlling Gs-versus-Gq preference and polypharmacology.

    Evidence Multiple independent cryo-EM datasets of human/mouse TAAR1-G protein complexes with mutagenesis, functional cAMP/Gq assays, and molecular dynamics

    PMID:37935376 PMID:37935377 PMID:37963465

    Open questions at the time
    • Structures capture surface-engaged states rather than intracellular signaling pools
    • Physiological relevance of Gq bias in vivo not established
  13. 2024 Medium

    Broadened TAAR1's roles across metabolism, immunity, and neuroprotection, showing β-cell insulin secretion, leukocyte/microglial responses, and BDNF-TrkB-dependent synaptic protection, plus central and peripheral control of glucose handling and feeding.

    Evidence β-cell line signaling assays; siRNA knockdown in leukocytes and HMC3 microglia with cytokine readouts; brain-slice OGD electrophysiology with TAAR1/TrkB inhibitors; DIO models with glucose, gastric emptying and whole-brain c-fos imaging; SEP-363856 (ulotaront) characterization with KO validation

    PMID:23315425 PMID:26302754 PMID:30670596 PMID:33482355 PMID:36100653 PMID:37511328 PMID:38237896

    Open questions at the time
    • Several peripheral findings lack genetic KO validation of TAAR1 specificity
    • Endogenous agonists in immune and metabolic tissues not defined
    • Causal contribution of intracellular vs surface TAAR1 pools to these effects unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How extracellular and amphetamine ligands access the intracellular TAAR1 pool, and how the structurally defined Gs/Gq bias maps onto the compartmentalized Gα13/GαS signaling and tissue-specific physiology, remains unresolved.
  • No unified model linking subcellular pools, G-protein selectivity, and behavioral/peripheral outputs
  • Endogenous physiological agonist in each tissue uncertain

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 2 GO:0005783 endoplasmic reticulum 1 GO:0005829 cytosol 1
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-162582 Signal Transduction 4 R-HSA-1430728 Metabolism 3 R-HSA-168256 Immune System 3
Partners
DRD2GNA13GNAS
Complex memberships
TAAR1-D2L receptor heteromer

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 Addition of an N-terminal asparagine-linked glycosylation site to human TAAR1 is sufficient to enable its plasma membrane expression in model cell systems (normally retained intracellularly), allowing pharmacological characterization; membrane-expressed human TAAR1 signals via cAMP elevation upon agonist stimulation, confirmed using a BRET-based cAMP/EPAC biosensor. N-terminal glycosylation-tag engineering, stable cell line expression, BRET cAMP biosensor assay Molecular pharmacology High 18524885
2009 TAAR1 activates an inwardly rectifying K+ current (Kir channel) in dopamine neurons of the ventral tegmental area; tonic TAAR1 activation reduces basal firing frequency of VTA dopamine neurons, demonstrated with selective antagonist EPPTB and confirmed absent in Taar1 knockout mice. Selective antagonist (EPPTB) pharmacology, whole-cell patch-clamp electrophysiology in mouse brain slices, Taar1 knockout validation Proceedings of the National Academy of Sciences of the United States of America High 19892733
2009 Species-specific ligand selectivity of rat vs. mouse TAAR1 is determined by non-conserved residues in transmembrane helices 4 (position 4.56) and 7 (position 7.39); residue 7.39 dictates preference for a beta-phenyl ring and residue 4.56 partly controls potency of 3-iodothyronamine and tyramine at mouse TAAR1. Site-directed mutagenesis of rat and mouse TAAR1, functional cAMP assays in transfected cells ACS chemical biology High 19256523
2011 TAAR1 agonism inhibits firing of dopaminergic neurons in the VTA and serotonergic neurons in the dorsal raphe nucleus (areas expressing TAAR1) but does not alter firing of noradrenergic neurons in locus coeruleus (area lacking TAAR1 expression); TAAR1 modulates desensitization rate and agonist potency at 5-HT1A receptors in the dorsal raphe, indicating cross-talk between TAAR1 and 5-HT1A signaling. Selective agonist RO5166017, electrophysiology in mouse brain slices, Taar1 knockout comparison, behavioral pharmacology Proceedings of the National Academy of Sciences of the United States of America High 21525407
2014 TAAR1 modulates presynaptic dopamine release in the nucleus accumbens by potentiating D2 autoreceptor-mediated inhibition: TAAR1 agonist RO5166017 decreased evoked DA release in WT but not TAAR1-KO mice, and enhanced quinpirole-induced D2 autoreceptor inhibition; TAAR1-KO mice showed reduced D2 autoreceptor short-term plasticity, without effects on dopamine clearance via DAT. Fast-scan cyclic voltammetry, in vivo microdialysis, TAAR1 agonist/antagonist pharmacology, TAAR1 knockout mice Neuropharmacology High 24565640
2015 TAAR1 forms a functional heteromeric complex with dopamine D2L receptor (D2R) in heterologous cells and in native brain tissue; TAAR1-D2R interaction alters TAAR1 subcellular localization, increases D2R agonist binding affinity, reduces β-arrestin 2 recruitment to D2R, and shifts TAAR1 signaling from Gαs/cAMP toward β-arrestin 2-dependent pathway, resulting in reduced GSK3β activation. Co-immunoprecipitation (heterologous cells and brain tissue), β-arrestin 2 complementation assay, cAMP BRET assay, TAAR1 KO and overexpressing rats, selective agonists European neuropsychopharmacology High 26372541
2015 TAAR1 loss in mice alters NMDA receptor subunit composition and reduces NMDA receptor functionality in pyramidal neurons of prefrontal cortex layer V; TAAR1-KO mice show dysregulated cortical glutamate transmission associated with perseverative and impulsive behavior, and TAAR1 agonists reduce premature impulsive responses. TAAR1 knockout mice, electrophysiology, NMDA receptor subunit quantification, behavioral testing, selective TAAR1 agonists Neuropsychopharmacology High 25749299
2015 TAAR1 loss produces postsynaptic D2 dopamine receptor supersensitivity in the striatum: TAAR1-KO mice have elevated D2 receptor mRNA and protein, selectively activated AKT/GSK3β G-protein-independent signaling (decreased phospho-AKT, decreased phospho-GSK3β), increased AKT/PP2A complex (co-IP), and enhanced locomotor response to D2 agonist quinpirole but not D1 agonist. TAAR1 knockout mice, quantitative RT-PCR, Western blot, co-immunoprecipitation (AKT/PP2A), locomotor pharmacology Neuropharmacology High 25721394
2019 TAAR1 is an obligate intracellular GPCR in dopamine neurons that couples to two distinct Gα subunits in separate subcellular compartments: intracellular TAAR1 couples to Gα13 near the endoplasmic reticulum to activate RhoA, and to GαS throughout the cell to activate PKA/cAMP. Amphetamine-induced RhoA and PKA signaling are abolished in TAAR1-knockout cells/mice and restored by small cell-permeable peptide inhibitors of G13 and GS respectively. TAAR1 knockout cell lines and mouse lines, RhoA-FRET and PKA-FRET sensors targeted to subcellular compartments, cell-permeable Gα-inhibitory peptides, in vivo pharmacology Molecular psychiatry High 31399635
2019 In pancreatic β-cells, TAAR1 couples to Gαs to activate PKA- and Epac-dependent insulin secretion, Raf-MAPK/ERK signaling, CREB-IRS-2 induction, and β-cell proliferation; TAAR1 activation also triggers cAMP-mediated calcium influx and release from internal stores, with CaMKII-Raf-MEK1/2 cascade required for MAPK activation. TAAR1 agonist treatment of insulin-secreting β-cell lines, cAMP assays, kinase inhibitors, proliferation assays, insulin secretion measurement The Journal of biological chemistry Medium 30670596
2018 In striatal dopaminergic neurons, T1AM activates TAAR1 to phosphorylate tyrosine hydroxylase at Ser19 (via CaMKII) and Ser40 (via PKA), promoting TH functional activity and increasing evoked dopamine release; this effect was absent in TAAR1-KO mice and blocked by TAAR1 antagonist EPPTB. In contrast, tyramine and β-PEA reduced Ser40-TH phosphorylation and these effects were NOT blocked in TAAR1-KO mice, indicating TAAR1-independent mechanisms. Western blot (TH phosphorylation), HPLC (DOPA accumulation), amperometry (evoked DA release), CaMKII inhibitor (KN-92), PKA inhibitor (H-89), TAAR1-KO mice, EPPTB antagonist, mass spectrometry imaging Frontiers in pharmacology High 29545750
2023 Cryo-EM structures of human and mouse TAAR1 in complex with diverse ligands (3-iodothyronamine, amphetamine, catecholamine agonists, antipsychotic agents) reveal a rigid primary amine recognition pocket (PARP) with conserved acidic residue D3.32 for amine recognition, a 'twin' toggle switch for receptor activation, and a second binding pocket (SBP) that determines signaling preference (Gs vs Gq). Targeting specific SBP residues modulates signaling bias; Gq activation by EAMs or synthetic compounds was also demonstrated. Cryo-electron microscopy (9 structures), site-directed mutagenesis, functional cAMP/Gq assays, molecular dynamics simulations Cell High 37963465
2023 Cryo-EM structures of human TAAR1-Gs complexes bound to methamphetamine, β-PEA, RO5256390, and SEP-363856 identify a lid-like extracellular loop 2 helix/loop structure and a hydrogen-bonding network in ligand-binding pockets critical for ligand recognition; systematic mutagenesis confirms the molecular basis of methamphetamine recognition and polypharmacology between TAAR1 and other monoamine receptors. Cryo-electron microscopy (4 structures of human TAAR1), systematic mutagenesis, functional assays Nature High 37935377
2023 Nine cryo-EM structures of human and mouse TAAR1 in complex with endogenous and synthetic ligands reveal a consensus binding motif for trace amine stimuli and two extended binding pockets accommodating diverse chemotypes; species-specific differences between human and mouse TAAR1 are structurally elucidated. Cryo-electron microscopy (9 structures), mutational analysis, functional assays, molecular dynamics simulations Nature High 37935376
2006 Human TAAR1 signals through cAMP elevation (Gαs coupling) upon stimulation by β-phenylethylamine (EC50 ~106 nM) and related trace amines; the pharmacological profile is distinct from classical monoaminergic receptors; species differences in agonist potency exist between rat and human TAAR1. Stable expression of HA-tagged human TAAR1 with rat Gαs in AV12-664 cells, cAMP accumulation assay, pharmacological profiling The Journal of pharmacology and experimental therapeutics Medium 17038507
2013 TAAR1 is functionally expressed in human blood PMN granulocytes and T and B lymphocytes; TAAR1 (and TAAR2) activation by 2-PEA, tyramine, and T1AM drives chemosensory migration of PMN, cytokine secretion by T cells, and immunoglobulin secretion by B cells; siRNA knockdown of TAAR1 abolished these amine-induced leukocyte functions. siRNA knockdown, migration assays, ELISA (cytokine/Ig), mRNA expression profiling in isolated human blood leukocyte populations Journal of leukocyte biology Medium 23315425
2016 LSD decreases VTA dopamine neuron firing at high doses through a mechanism involving TAAR1 (in addition to D2 and 5-HT1A receptors): pretreatment with TAAR1 antagonist EPPTB blocked LSD's inhibitory effect on VTA DA neuron firing in vivo. In vivo single-unit electrophysiology in anesthetized rats, pharmacological antagonism (EPPTB, haloperidol, WAY-100635), 5-HT depletion with PCPA Pharmacological research Medium 27544651
2018 Taar1 is required for canonical TSH regulation of thyroglobulin processing in the thyroid: Taar1-KO mice show elevated TSH, mislocalized TSH receptors (intracellular rather than basolateral), luminal accumulation of covalently cross-linked thyroglobulin, decreased cathepsin proteolytic activity, and upregulated cystatins, indicating Taar1 participates in the proteolytic network controlling thyroid hormone synthesis. Taar1 knockout mice, serum hormone measurement (T4, T3, TSH), immunofluorescence (TSH receptor localization), enzymatic activity assays (cathepsins), immunohistochemistry Frontiers in pharmacology Medium 29615904
2015 TAAR1 loss increases context-dependent conditioned locomotor sensitization and priming-induced reinstatement of amphetamine CPP; TAAR1-KO mice show altered total levels and phosphorylation of GluN1 (NMDA receptor subunit) in striatum, suggesting TAAR1 modulates corticostriatal glutamate transmission. TAAR1 knockout mice, conditioned place preference, locomotor sensitization, Western blot (GluN1 phosphorylation) Pharmacological research Medium 26640076
2020 Tyramine accumulation following MAO inhibition acts via TAAR1 to reduce glutamate release in the substantia nigra; TAAR1-KO mice show higher striatal tyramine accumulation after tranylcypromine, suggesting TAAR1 provides negative feedback on tyramine levels. TAAR1 localization was identified in brain areas projecting to the substantia nigra/VTA. TAAR1-KO mice, enzyme-based biosensor for glutamate in freely moving animals, mass spectrometry imaging (tyramine), histoenzymological and immunohistological localization Biological psychiatry Medium 33579534
2019 Taar1 has a causal role in methamphetamine intake and thermal response: CRISPR-Cas9 correction of the non-functional Taar1 mutation in DBA/2J mice rescued methamphetamine avoidance and normalized the thermal response to methamphetamine; the effect of Taar1 on methamphetamine intake is genetically epistatic to Oprm1 (mu-opioid receptor) genotype. CRISPR-Cas9 mutagenesis/rescue, recombinant inbred strain interval mapping, genetic epistasis analysis, behavioral phenotyping eLife High 31274109
2022 SEP-363856 (ulotaront) activates TAAR1 at the plasma membrane, recruits Gαs, and activates GIRK (G protein inwardly rectifying potassium) channels; TAAR1 is required for SEP-363856's effects on body temperature, baseline locomotion reduction, and reversal of MK-801-induced PPI disruption, as demonstrated by absence of these effects in TAAR1-KO mice. Luciferase complementation-based G protein recruitment assays, cAMP accumulation, GIRK voltage-clamp electrophysiology, TAAR1-KO mice, confocal microscopy Neuropsychopharmacology High 36100653
2015 In T lymphocytes, methamphetamine-induced cAMP elevation and IL-2 downregulation are regulated via TAAR1, as demonstrated by TAAR1 gene silencing (siRNA knockdown abolishing these effects). siRNA knockdown of TAAR1 in human T lymphocytes, cAMP assay, IL-2 ELISA, immunofluorescence Journal of leukocyte biology Medium 26302754
2018 Naturally occurring missense variants in human TAAR1 (p.Arg23Cys, p.Ser49Leu) cause partial (S49L) or complete (R23C) loss of function in cAMP signaling and cell surface expression in vitro, identifying functionally critical residues for receptor activity and potential links to glucose homeostasis and weight regulation. In vitro functional characterization of TAAR1 SNP variants (cAMP assays, cell surface expression assays) in transfected cells Frontiers in pharmacology Medium 29225575
2024 TAAR1 agonists improve oral glucose tolerance by inhibiting gastric emptying; central TAAR1 activation increases neuronal activity in homeostatic and hedonic feeding centers (dorsal vagal complex, hypothalamus, limbic structures) as shown by whole-brain c-fos imaging, indicating both peripheral and central mechanisms for metabolic effects. Diet-induced obesity mouse/rat models, glucose tolerance test, gastric emptying assay, whole-brain c-fos immunofluorescence imaging, TAAR1 agonist treatment (ulotaront, RO5166017, RO5263397) Molecular metabolism Medium 38237896
2021 T1AM activates TAAR1 to protect against OGD-induced synaptic depression in the entorhinal cortex; this neuroprotection requires BDNF-TrkB signaling downstream of TAAR1, demonstrated by blocking T1AM's effect with a TAAR1 antagonist and TrkB inhibitor in brain slices. Ex vivo brain slice LTP/synaptic depression recordings under OGD conditions, TAAR1 antagonist pharmacology, TrkB inhibitor, mhAPP transgenic mice Neurobiology of disease Medium 33482355
2023 T1AM reduces inflammatory responses in human microglial HMC3 cells via TAAR1: siRNA knockdown of TAAR1 abolished T1AM-induced reduction of IL-6, TNFα, NF-kB, MCP1, MIP1 and increase of IL-10 following LPS/TNFα or β-amyloid stimulation. siRNA knockdown of TAAR1, ELISA (cytokine measurement), qPCR, human microglial cell line (HMC3) International journal of molecular sciences Medium 37511328

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1984 Ta1, a novel 105 KD human T cell activation antigen defined by a monoclonal antibody. Journal of immunology (Baltimore, Md. : 1950) 290 6205075
2011 TAAR1 activation modulates monoaminergic neurotransmission, preventing hyperdopaminergic and hypoglutamatergic activity. Proceedings of the National Academy of Sciences of the United States of America 278 21525407
2012 A new perspective for schizophrenia: TAAR1 agonists reveal antipsychotic- and antidepressant-like activity, improve cognition and control body weight. Molecular psychiatry 223 22641180
2009 The selective antagonist EPPTB reveals TAAR1-mediated regulatory mechanisms in dopaminergic neurons of the mesolimbic system. Proceedings of the National Academy of Sciences of the United States of America 186 19892733
1995 Transactivation domain 2 (TA2) of p65 NF-kappa B. Similarity to TA1 and phorbol ester-stimulated activity and phosphorylation in intact cells. The Journal of biological chemistry 154 7797554
2018 The Case for TAAR1 as a Modulator of Central Nervous System Function. Frontiers in pharmacology 125 29375386
2008 Pharmacological characterization of membrane-expressed human trace amine-associated receptor 1 (TAAR1) by a bioluminescence resonance energy transfer cAMP biosensor. Molecular pharmacology 118 18524885
2014 Taar1-mediated modulation of presynaptic dopaminergic neurotransmission: role of D2 dopamine autoreceptors. Neuropharmacology 116 24565640
1986 Antigen reactive memory T cells are defined by Ta1. Journal of immunology (Baltimore, Md. : 1950) 107 3013990
2015 Trace amine-associated receptor 1 activation silences GSK3β signaling of TAAR1 and D2R heteromers. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 100 26372541
2015 TAAR1 Modulates Cortical Glutamate NMDA Receptor Function. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 99 25749299
2013 Biogenic amines activate blood leukocytes via trace amine-associated receptors TAAR1 and TAAR2. Journal of leukocyte biology 98 23315425
1980 A monoclonal antibody (TA-1) reactive with human T lymphocytes and monocytes. Journal of immunology (Baltimore, Md. : 1950) 91 6968776
2016 The hallucinogen d-lysergic diethylamide (LSD) decreases dopamine firing activity through 5-HT1A, D2 and TAAR1 receptors. Pharmacological research 86 27544651
2006 Pharmacologic characterization of the cloned human trace amine-associated receptor1 (TAAR1) and evidence for species differences with the rat TAAR1. The Journal of pharmacology and experimental therapeutics 85 17038507
1996 Expression of a highly conserved oncofetal gene, TA1/E16, in human colon carcinoma and other primary cancers: homology to Schistosoma mansoni amino acid permease and Caenorhabditis elegans gene products. Cancer research 81 8895758
2021 Therapeutic Potential of TAAR1 Agonists in Schizophrenia: Evidence from Preclinical Models and Clinical Studies. International journal of molecular sciences 80 34947997
2015 Postsynaptic D2 dopamine receptor supersensitivity in the striatum of mice lacking TAAR1. Neuropharmacology 79 25721394
1995 TA1, a highly conserved oncofetal complementary DNA from rat hepatoma, encodes an integral membrane protein associated with liver development, carcinogenesis, and cell activation. Cancer research 76 7532544
2019 Amphetamines signal through intracellular TAAR1 receptors coupled to Gα13 and GαS in discrete subcellular domains. Molecular psychiatry 72 31399635
2022 Trace amine-associated receptor 1 (TAAR1) agonism as a new treatment strategy for schizophrenia and related disorders. Trends in neurosciences 67 36369028
1998 The light chain of CD98 is identified as E16/TA1 protein. The Journal of biological chemistry 66 9837878
1989 Increment in the Ta1+ cells in the peripheral blood and thyroid tissue of patients with Graves' disease. Journal of immunology (Baltimore, Md. : 1950) 59 2542405
1990 FcR-mediated crosslinking of Ta1 (CDw26) induces human T lymphocyte activation. Cellular immunology 55 2152856
1989 Mechanisms of immune memory. T cell activation and CD3 phosphorylation correlates with Ta1 (CDw26) expression. Journal of immunology (Baltimore, Md. : 1950) 52 2564857
2023 Ligand recognition and G-protein coupling of trace amine receptor TAAR1. Nature 51 37935376
2022 Role of 5-HT2A, 5-HT2C, 5-HT1A and TAAR1 Receptors in the Head Twitch Response Induced by 5-Hydroxytryptophan and Psilocybin: Translational Implications. International journal of molecular sciences 51 36430623
2021 Ulotaront: A TAAR1 Agonist for the Treatment of Schizophrenia. ACS medicinal chemistry letters 51 35047111
2000 TA1/LAT-1/CD98 light chain and system L activity, but not 4F2/CD98 heavy chain, respond to arginine availability in rat hepatic cells. Loss Of response in tumor cells. The Journal of biological chemistry 50 10681508
2023 Structural and signaling mechanisms of TAAR1 enabled preferential agonist design. Cell 45 37963465
2012 Optimisation of imidazole compounds as selective TAAR1 agonists: discovery of RO5073012. Bioorganic & medicinal chemistry letters 42 22795332
2020 Trace Amine-Associated Receptor 1 (TAAR1): A new drug target for psychiatry? Neuroscience and biobehavioral reviews 41 33031817
2019 Trace amine-associated receptor 1 (TAAR1) promotes anti-diabetic signaling in insulin-secreting cells. The Journal of biological chemistry 41 30670596
1990 Excessive excretion of cyclic beta-(1,2)-glucan by Rhizobium trifolii TA-1. Applied and environmental microbiology 41 2117876
2019 Actions of Trace Amines in the Brain-Gut-Microbiome Axis via Trace Amine-Associated Receptor-1 (TAAR1). Cellular and molecular neurobiology 40 31836967
2023 Recognition of methamphetamine and other amines by trace amine receptor TAAR1. Nature 39 37935377
2017 Role of TAAR1 within the Subregions of the Mesocorticolimbic Dopaminergic System in Cocaine-Seeking Behavior. The Journal of neuroscience : the official journal of the Society for Neuroscience 39 28123023
2023 Ulotaront: review of preliminary evidence for the efficacy and safety of a TAAR1 agonist in schizophrenia. European archives of psychiatry and clinical neuroscience 38 37165101
2017 New Insights into the Potential Roles of 3-Iodothyronamine (T1AM) and Newly Developed Thyronamine-Like TAAR1 Agonists in Neuroprotection. Frontiers in pharmacology 38 29311919
2009 The molecular basis of species-specific ligand activation of trace amine-associated receptor 1 (TAAR(1)). ACS chemical biology 38 19256523
1988 Tissue distribution of the T cell activation antigen Ta1. Serological, immunohistochemical and biochemical investigations. Clinical and experimental immunology 37 2466591
2016 Novel biguanide-based derivatives scouted as TAAR1 agonists: Synthesis, biological evaluation, ADME prediction and molecular docking studies. European journal of medicinal chemistry 36 27823885
2021 Effect of TAAR1/5-HT1A agonist SEP-363856 on REM sleep in humans. Translational psychiatry 35 33879769
2014 TAAR1-dependent effects of apomorphine in mice. The international journal of neuropsychopharmacology 35 24925023
2018 TAAR1 in Addiction: Looking Beyond the Tip of the Iceberg. Frontiers in pharmacology 34 29636691
2018 A Spontaneous Mutation in Taar1 Impacts Methamphetamine-Related Traits Exclusively in DBA/2 Mice from a Single Vendor. Frontiers in pharmacology 33 29403379
1983 Preliminary structural characterization of the leukocyte cell surface molecule recognized by monoclonal antibody TA-1. Journal of immunology (Baltimore, Md. : 1950) 33 6601140
2021 Trace amine-associated receptor 1 (TAAR1): Potential application in mood disorders: A systematic review. Neuroscience and biobehavioral reviews 31 34537265
2020 TAAR1 and Psychostimulant Addiction. Cellular and molecular neurobiology 31 31974906
2003 Membrane topology of PssT, the transmembrane protein component of the type I exopolysaccharide transport system in Rhizobium leguminosarum bv. trifolii strain TA1. Journal of bacteriology 31 12670974
1994 Thermophilic Alkaline Xylanase from Newly Isolated Alkaliphilic and Thermophilic Bacillus sp. Strain TAR-1. Bioscience, biotechnology, and biochemistry 31 27315708
2022 TAAR1 dependent and independent actions of the potential antipsychotic and dual TAAR1/5-HT1A receptor agonist SEP-383856. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 30 36100653
2018 Biochemical and Functional Characterization of the Trace Amine-Associated Receptor 1 (TAAR1) Agonist RO5263397. Frontiers in pharmacology 30 29977204
2017 Increased trace amine-associated receptor 1 (TAAR1) expression is associated with a positive survival rate in patients with breast cancer. Journal of cancer research and clinical oncology 30 28409272
2018 Rational design, chemical synthesis and biological evaluation of novel biguanides exploring species-specificity responsiveness of TAAR1 agonists. European journal of medicinal chemistry 29 29407948
2014 Further insights into the pharmacology of the human trace amine-associated receptors: discovery of novel ligands for TAAR1 by a virtual screening approach. Chemical biology & drug design 29 24894156
1998 Molecular characterization of pssCDE genes of Rhizobium leguminosarum bv. trifolii strain TA1: pssD mutant is affected in exopolysaccharide synthesis and endocytosis of bacteria. Molecular plant-microbe interactions : MPMI 29 9805402
2015 Increased context-dependent conditioning to amphetamine in mice lacking TAAR1. Pharmacological research 28 26640076
2023 Multiplex CRISPR/Cas9-mediated mutagenesis of alfalfa FLOWERING LOCUS Ta1 (MsFTa1) leads to delayed flowering time with improved forage biomass yield and quality. Plant biotechnology journal 27 36964962
1990 Binding of the T cell activation monoclonal antibody Ta1 to dipeptidyl peptidase IV. Journal of leukocyte biology 27 1975616
2021 Binding of SEP-363856 within TAAR1 and the 5HT1A receptor: implications for the design of novel antipsychotic drugs. Molecular psychiatry 26 34376825
2010 Functional evolution of the trace amine associated receptors in mammals and the loss of TAAR1 in dogs. BMC evolutionary biology 26 20167089
2022 Effects of acute and chronic administration of trace amine-associated receptor 1 (TAAR1) ligands on in vivo excitability of central monoamine-secreting neurons in rats. Molecular psychiatry 25 36045279
2005 Topological and transcriptional analysis of pssL gene product: a putative Wzx-like exopolysaccharide translocase in Rhizobium leguminosarum bv. trifolii TA1. Archives of microbiology 25 16044265
2022 Trace Amine-Associated Receptor 1 (TAAR1): Molecular and Clinical Insights for the Treatment of Schizophrenia and Related Comorbidities. ACS pharmacology & translational science 24 35311018
2019 Taar1 gene variants have a causal role in methamphetamine intake and response and interact with Oprm1. eLife 24 31274109
2021 TAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation. International journal of molecular sciences 23 34769007
2020 Novel 1-Amidino-4-Phenylpiperazines as Potent Agonists at Human TAAR1 Receptor: Rational Design, Synthesis, Biological Evaluation and Molecular Docking Studies. Pharmaceuticals (Basel, Switzerland) 23 33202687
2018 Canonical TSH Regulation of Cathepsin-Mediated Thyroglobulin Processing in the Thyroid Gland of Male Mice Requires Taar1 Expression. Frontiers in pharmacology 23 29615904
2015 Methamphetamine induces trace amine-associated receptor 1 (TAAR1) expression in human T lymphocytes: role in immunomodulation. Journal of leukocyte biology 23 26302754
2023 TAAR1 as an emerging target for the treatment of psychiatric disorders. Pharmacology & therapeutics 21 38142862
2021 Depicting Safety Profile of TAAR1 Agonist Ulotaront Relative to Reactions Anticipated for a Dopamine D2-Based Pharmacological Class in FAERS. Clinical drug investigation 21 34751928
2020 TAAR1 agonists attenuate extended-access cocaine self-administration and yohimbine-induced reinstatement of cocaine-seeking. British journal of pharmacology 21 32246467
2018 Review and Meta-Analyses of TAAR1 Expression in the Immune System and Cancers. Frontiers in pharmacology 21 29997511
2017 Investigation of Naturally Occurring Single-Nucleotide Variants in Human TAAR1. Frontiers in pharmacology 21 29225575
2023 T1AM/TAAR1 System Reduces Inflammatory Response and β-Amyloid Toxicity in Human Microglial HMC3 Cell Line. International journal of molecular sciences 20 37511328
1996 Cloning and sequence analysis of the candidate nicotinic acetylcholine receptor alpha subunit gene tar-1 from Trichostrongylus colubriformis. Gene 20 8982073
2016 Hypothesizing that, A Pro-Dopamine Regulator (KB220Z) Should Optimize, but Not Hyper-Activate the Activity of Trace Amine-Associated Receptor 1 (TAAR-1) and Induce Anti-Craving of Psychostimulants in the Long-Term. Journal of reward deficiency syndrome and addiction science 19 28317038
2024 TAAR1 agonists improve glycemic control, reduce body weight and modulate neurocircuits governing energy balance and feeding. Molecular metabolism 18 38237896
2023 In Vitro Comparison of Ulotaront (SEP-363856) and Ralmitaront (RO6889450): Two TAAR1 Agonist Candidate Antipsychotics. The international journal of neuropsychopharmacology 18 37549917
2019 Thyronamine regulation of TAAR1 expression in breast cancer cells and investigation of its influence on viability and migration. Breast cancer (Dove Medical Press) 18 30858725
2019 The Action of TAAR1 Agonist RO5263397 on Executive Functions in Rats. Cellular and molecular neurobiology 17 31734895
2019 Trace amine associated receptor 1 (TAAR1) modulators: a patent review (2010-present). Expert opinion on therapeutic patents 17 31865810
2018 Trace Amine Associated Receptor 1 (TAAR1) Modulation of Food Reward. Frontiers in pharmacology 17 29535626
2024 Trace amine-associated receptor 1 (TAAR1) agonism for psychosis: a living systematic review and meta-analysis of human and non-human data. Wellcome open research 16 39036710
2023 Fermented soybean foods (natto) ameliorate age-related cognitive decline by hippocampal TAAR1-mediated activation of the CaMKII/CREB/BDNF signaling pathway in senescence-accelerated mouse prone 8 (SAMP8). Food & function 16 37870125
2022 Trace Amine Associate Receptor 1 (TAAR1) as a New Target for the Treatment of Cognitive Dysfunction in Alzheimer's Disease. International journal of molecular sciences 16 35887159
2021 Monoterpenes alter TAR1-driven physiology in Drosophila species. The Journal of experimental biology 16 33234680
2024 TAAR1 in dentate gyrus is involved in chronic stress-induced impairments in hippocampal plasticity and cognitive function. Progress in neuro-psychopharmacology & biological psychiatry 15 38514038
2021 Ulotaront, a novel TAAR1 agonist with 5-HT1A agonist activity, lacks abuse liability and attenuates cocaine cue-induced relapse in rats. Drug and alcohol dependence 15 35033729
2020 TAAR1-Dependent and -Independent Actions of Tyramine in Interaction With Glutamate Underlie Central Effects of Monoamine Oxidase Inhibition. Biological psychiatry 15 33579534
2019 Trace amine associated receptor 1 (TAAR1) expression and modulation of inflammatory cytokine production in mouse bone marrow-derived macrophages: a novel mechanism for inflammation in ulcerative colitis. Immunopharmacology and immunotoxicology 15 31570011
2013 BRET approaches to characterize dopamine and TAAR1 receptor pharmacology and signaling. Methods in molecular biology (Clifton, N.J.) 15 23296781
2011 repABC-based replication systems of Rhizobium leguminosarum bv. trifolii TA1 plasmids: incompatibility and evolutionary analyses. Plasmid 15 21620885
2022 The Potential Antidepressant Action of Duloxetine Co-Administered with the TAAR1 Receptor Agonist SEP-363856 in Mice. Molecules (Basel, Switzerland) 14 35566106
2021 T1AM-TAAR1 signalling protects against OGD-induced synaptic dysfunction in the entorhinal cortex. Neurobiology of disease 14 33482355
2018 Striatal Tyrosine Hydroxylase Is Stimulated via TAAR1 by 3-Iodothyronamine, But Not by Tyramine or β-Phenylethylamine. Frontiers in pharmacology 14 29545750
2009 Negative roles of a novel nitrogen metabolite repression-related gene, TAR1, in laccase production and nitrate utilization by the basidiomycete Cryptococcus neoformans. Applied and environmental microbiology 14 19734333
1997 The nicotinic acetylcholine alpha-subunit gene tar-1 is located on the X chromosome but its coding sequence is not involved in levamisole resistance in an isolate of Trichostrongylus colubriformis. Molecular and biochemical parasitology 14 9476789
2019 TAAR1 levels and sub-cellular distribution are cell line but not breast cancer subtype specific. Histochemistry and cell biology 13 31111198

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