Affinage

Showing TACR1 — NK1R is a alias.

TACR1

Substance-P receptor · UniProt P25103

Length
407 aa
Mass
46.3 kDa
Annotated
2026-06-10
100 papers in source corpus 25 papers cited in narrative 25 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

TACR1 (NK1R) is a Gq/11-coupled receptor for substance P (SP) that converts neuropeptide signals into intracellular calcium and kinase cascades to drive neurotransmission, neurogenic inflammation, and pain/itch circuit function (PMID:9693383, PMID:30453005). SP binding engages two spatially proximal extracellular contact regions—the second extracellular loop (residues 173–177) and the N-terminus (residues 11–21)—and the N-terminus is also required for receptor surface targeting (PMID:11294866, PMID:29430989). Upon SP-induced calcium mobilization, the receptor rapidly desensitizes and is internalized into early endosomes through redistribution of beta-arrestin-1 and -2 to the plasma membrane and then to receptor-containing endosomes, while Gαq/11 remains at the membrane (PMID:9693383). Downstream of NK1R, SP activates ERK1/2 together with an IP3R/L-type Ca2+ channel–dependent PI3K/PKCα/βII–ERK1/2 and CaMKII/Akt cascade (PMID:30453005), and engages JNK, p38, and NF-κB arms in disease contexts (PMID:26645045, PMID:37033943). The receptor exists as full-length and truncated (NK1R-T/Tr) isoforms with distinct signaling outputs: the truncated form expressed on monocytes does not mobilize calcium alone but selectively activates ERK2 and amplifies CCL5/CCR5-mediated chemotaxis through CCR5 serine phosphorylation (PMID:18835883). In the CNS, NK1R constrains monoaminergic tone—its loss elevates prefrontal noradrenaline via desensitized locus coeruleus α2A-adrenoceptors and reduces prefrontal/striatal dopamine efflux—and modulates reward-related and alcohol-consumption behaviors (PMID:17331215, PMID:19204064, PMID:20112009, PMID:23419547). Spinal and brainstem Tacr1-expressing neurons form a circuit for sustained (but not acute) pain and bidirectional itch control, including a spino–parabrachial projection and RVM ON cells excited by SP (PMID:33591273, PMID:35972457). NK1R expression is transcriptionally induced by NF-κB downstream of inflammatory cytokines (PMID:12734344, PMID:15390113), by Smad4 downstream of TGFβ (PMID:32380077), and by TFAP4 (PMID:37033943), and SP/NK1R signaling drives perineural cancer invasion, tumor proliferation, microglial polarization, and renal fibrosis (PMID:23345604, PMID:29896303, PMID:31109645, PMID:34244927, PMID:37033943).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1998 High

    Established how NK1R signaling is terminated and recycled, defining a beta-arrestin-dependent desensitization and endocytic itinerary for the receptor.

    Evidence Calcium imaging, immunofluorescence and subcellular fractionation in cultured myenteric neurons

    PMID:9693383

    Open questions at the time
    • Does not resolve the GRK phosphorylation sites on NK1R
    • Resignaling vs degradation fate of internalized receptor not defined
  2. 2001 High

    Defined the structural topology of SP engagement, mapping two distinct extracellular ligand-contact regions on EC2 and the N-terminus.

    Evidence Photoaffinity labeling with radiolabeled SP analogue and peptide mapping in vitro

    PMID:11294866

    Open questions at the time
    • No full receptor structure or agonist-bound conformational model
    • Functional consequence of each contact site for activation not tested
  3. 2003 Medium

    Showed NK1R expression is inducible rather than fixed, placing it downstream of inflammatory cytokine signaling via NF-κB on immune cells.

    Evidence Murine splenocyte cytokine culture with NF-κB inhibitors and Stat4-/- mice, RT-PCR

    PMID:12734344

    Open questions at the time
    • NF-κB binding site on the TACR1 promoter not mapped here
    • Whether induced receptor is functional not tested in this study
  4. 2004 Medium

    Extended cytokine-driven NF-κB induction of NK1R to CNS glia and confirmed the induced receptor is functionally coupled to calcium signaling.

    Evidence Western blot, RT-PCR, Ca2+ imaging, NF-κB luciferase reporter and antagonist blockade in astroglioma and primary astrocytes

    PMID:15390113

    Open questions at the time
    • Direct promoter occupancy by NF-κB not shown
    • Single-lab pharmacological evidence
  5. 2005 Medium

    Placed NK1R downstream of TRPV1 in a neurogenic inflammation pathway in vivo, linking nociceptor activation to SP-mediated plasma extravasation.

    Evidence Evans blue extravasation with TRPV1 and NK1R antagonists in rat pancreas

    PMID:15782105

    Open questions at the time
    • Pharmacological only, no genetic confirmation
    • Cellular source of SP not defined
  6. 2007 High

    Revealed a homeostatic role for NK1R in restraining noradrenergic transmission through α2A-adrenoceptor desensitization in the locus coeruleus.

    Evidence In vivo microdialysis, [35S]GTPγS binding and Western blot in NK1R-/- vs wildtype mice

    PMID:17331215

    Open questions at the time
    • Mechanism linking NK1R loss to α2A desensitization not resolved
    • Direct vs developmental effect of constitutive KO unclear
  7. 2009 High

    Demonstrated NK1R control of dopaminergic tone and the behavioral consequences, connecting receptor loss to a psychostimulant-reversible hyperactivity phenotype.

    Evidence In vivo microdialysis and locomotor/psychostimulant rescue in NK1R-/- mice

    PMID:19204064

    Open questions at the time
    • Circuit locus of dopaminergic modulation not pinpointed
    • Constitutive KO cannot distinguish developmental compensation
  8. 2010 High

    Implicated NK1R in alcohol reward and consumption using converging genetic and pharmacological loss-of-function.

    Evidence Two-bottle choice, conditioned place preference with NK1R KO and antagonist verified in KO controls

    PMID:20112009

    Open questions at the time
    • Brain locus not identified in this study
    • Downstream signaling not addressed
  9. 2013 Medium

    Localized the alcohol phenotype to the central amygdala and identified a functional promoter SNP altering transcription-factor binding and NK1R expression.

    Evidence Operant self-administration with central amygdala microinfusion, receptor binding, EMSA and luciferase in alcohol-preferring rats

    PMID:23419547

    Open questions at the time
    • GATA-2/E2F-1 occupancy shown in vitro only
    • Causal link from SNP to behavior not directly tested
  10. 2008 High

    Distinguished a truncated NK1R isoform with a separate signaling output that amplifies chemokine receptor function on immune cells.

    Evidence Calcium, chemotaxis, ERK and CCR5 phosphorylation assays with isoform-specific transfection in monocytes

    PMID:18835883

    Open questions at the time
    • Structural basis of CCR5 crosstalk not defined
    • In vivo relevance of monocyte NK1R-T not established
  11. 2011 Medium

    Mapped NK1R coupling to both contractile (MLC20) and pro-inflammatory (p38/ERK) outputs with PKC-dependent crosstalk in lymphatic muscle, and to adipose insulin signaling.

    Evidence Pharmacological inhibition with phosphoprotein Western blots; NK1R KO high-fat-diet metabolic phenotyping and adipocyte glucose uptake

    PMID:21166923 PMID:21467195

    Open questions at the time
    • Receptor identity in lymphatic cells confirmed pharmacologically only
    • Tissue-specific contribution of NK1R to metabolism not isolated
  12. 2015 Medium

    Defined a protective SP/NK1R/miR-221-5p/IL-6R axis in colonic epithelium, linking NK1R to NF-κB/JNK-driven post-transcriptional control.

    Evidence miRNA profiling, luciferase target validation, pathway inhibitors and TNBS/DSS colitis models

    PMID:26645045

    Open questions at the time
    • Single-lab in vivo models
    • Generalizability beyond colonic epithelium unknown
  13. 2018 Medium

    Established SP/NK1R as a driver of perineural cancer invasion via an MMP1/PAR1/SP relay and downstream ERK signaling, and uncovered a physical NK1R–5-HT1AR interaction governing melanogenesis.

    Evidence DRG-tumor coculture and sciatic nerve invasion models with shRNA/antagonists; co-IP, N-terminal deletion mutagenesis and zebrafish/mouse melanin models

    PMID:29430989 PMID:29896303

    Open questions at the time
    • Direct vs indirect NK1R–5-HT1AR contact interface not mapped
    • Stoichiometry and signaling output of the heteromer unclear
  14. 2019 Medium

    Identified Hes1 as a proliferative effector downstream of SP/NK1R in esophageal carcinoma.

    Evidence iTRAQ proteomics, proliferation/colony assays and xenografts with NK1R knockdown

    PMID:31109645

    Open questions at the time
    • Mechanism linking NK1R to Hes1 induction not resolved
    • Single-lab finding
  15. 2021 High

    Defined Tacr1-expressing spinal and parabrachial circuits selective for sustained pain, distinguishing ongoing from acute nociception.

    Evidence Optogenetic activation of spinal Tacr1 neurons and chemogenetic silencing of PBN-SL Tacr1 neurons with optotagging and behavior

    PMID:33591273

    Open questions at the time
    • Role of NK1R signaling itself (vs cell identity marker) within the circuit not isolated
    • Synaptic basis of sustained-stimulus selectivity unclear
  16. 2021 Medium

    Linked neuronal NK1R to neuroinflammatory injury, showing aprepitant suppresses NLRC4-dependent pyroptosis via NK1R/PKCδ and shifts microglia toward M2 polarization after hemorrhage.

    Evidence Mouse ICH models with agonist/siRNA epistasis, Western blot and immunofluorescence

    PMID:34244927 PMID:35922848

    Open questions at the time
    • Direct NK1R-to-NLRC4/PKCδ coupling mechanism not defined
    • Single-lab models
  17. 2022 High

    Showed Tacr1 RVM ON cells provide descending inhibitory control of itch, complementing the parabrachial pain circuit.

    Evidence Intramedullary SP, chemogenetic activation and optotagging electrophysiology with itch/pain behavior

    PMID:35972457

    Open questions at the time
    • Downstream spinal targets of RVM Tacr1 ON cells not mapped
    • Interaction with ascending Tacr1 pain circuit untested
  18. 2020 Medium

    Established direct transcriptional control of NK1R by Smad4 downstream of TGFβ and by TFAP4, with the truncated isoform driving tumor proliferation and renal profibrotic programs.

    Evidence ChIP, promoter mutagenesis and dual-luciferase assays with KO/overexpression in breast cancer and kidney (UUO) models

    PMID:32380077 PMID:37033943

    Open questions at the time
    • Isoform-selective promoter usage not fully resolved
    • Cross-regulation among NF-κB, Smad4 and TFAP4 inputs unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the differential signaling of full-length versus truncated NK1R isoforms is allocated across tissues, and how isoform expression is selectively controlled by the converging NF-κB/Smad4/TFAP4 transcriptional inputs, remains unresolved.
  • No structural model linking isoform truncation to biased signaling
  • Promoter elements distinguishing full-length vs truncated transcription not defined
  • In vivo isoform-specific genetic tools lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 2 GO:0048018 receptor ligand activity 1
Localization
GO:0005886 plasma membrane 2 GO:0005768 endosome 1
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
ARRB1ARRB2CCR5GNAQHTR1ATAC1

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Substance P (SP) induces desensitization and endocytosis of NK1R in myenteric neurons: SP causes rapid NK1R-mediated increase in [Ca2+]i that desensitizes to repeated stimulation, internalizes NK1R into early endosomes containing SP, and triggers rapid redistribution of beta-arrestin-1 and -2 from cytosol to plasma membrane and then to endosomes containing NK1R and SP. GRK-2 and GRK-3 remain in vesicles while Galphaq/11 stays at the plasma membrane. Calcium imaging, immunofluorescence, subcellular fractionation in cultured myenteric neurons Molecular biology of the cell High 9693383
2001 Photolabeling of NK1R with p-benzoylphenylalanine3-SP (Bpa3-SP) demonstrates spatial proximity between two distinct extracellular receptor regions in the SP·NK1R complex: one site on the second extracellular loop (EC2) within residues 173–177, and a second site on the extracellular N-terminus within residues 11–21 (containing potential N-linked glycosylation sites). Photoaffinity labeling with radiolabeled SP analogue, peptide mapping The Journal of biological chemistry High 11294866
2003 IL-12 and IL-18 induce NK1R expression on T cells through NF-κB activation (requiring NF-κB nuclear translocation but not the Stat4 pathway), and this induction is blocked by IL-10 but not TGF-β. Murine splenocyte culture with cytokines, actinomycin D/cycloheximide treatment, NF-κB inhibitors, Stat4-/- mice, RT-PCR Journal of immunology Medium 12734344
2004 IL-1β upregulates NK1R expression in human astroglioma cells and primary rat astrocytes through NF-κB activation; the induced NK1R is functional as demonstrated by SP-stimulated Ca2+ mobilization, which is inhibited by the NK1R antagonist CP-96,345. Western blot, RT-PCR, Ca2+ imaging, NF-κB luciferase reporter assay, CAPE inhibitor of NF-κB Glia Medium 15390113
2005 Activation of TRPV-1 by capsaicin induces SP-mediated plasma extravasation in the rat pancreas via NK1R, as shown by blockade with either the TRPV-1 antagonist capsazepine or the NK1R antagonist CP 96,345. Evans blue extravasation assay, pharmacological antagonist blockade in vivo Pancreas Medium 15782105
2007 NK1R knockout mice show two-to-fourfold greater extracellular noradrenaline in the prefrontal cortex compared to wildtypes due to increased transmitter release coupled with desensitization of somatodendritic alpha2a-adrenoceptors in the locus coeruleus (reduced [35S]GTPγS binding to alpha2a-adrenoceptors by ~70% in locus coeruleus of NK1R-/- mice), establishing that NK1R normally constrains noradrenergic transmission. In vivo microdialysis, [35S]GTPγS binding, Western blot for noradrenaline transporter, alpha2-adrenoceptor pharmacology The European journal of neuroscience High 17331215
2008 Human peripheral blood monocytes express the truncated NK1R isoform (NK1R-T) but not full-length NK1R. NK1R-T does not mobilize Ca2+ on its own but selectively activates ERK2 and enhances CCL5/CCR5-mediated Ca2+ mobilization and chemotaxis in an ERK1/2-dependent manner. NK1R-T activation also causes serine phosphorylation of CCR5, indicating receptor crosstalk. Western blot, Ca2+ mobilization assay, chemotaxis (Transwell), ERK phosphorylation assay, NK1R-F transfection comparison Journal of leukocyte biology High 18835883
2009 NK1R deficiency (genetic knockout) leads to reduced spontaneous dopamine efflux (>50%) in prefrontal cortex and abolishes the striatal dopamine response to d-amphetamine, as shown by in vivo microdialysis; locomotor hyperactivity from NK1R inactivation is reversed by psychostimulants methylphenidate and d-amphetamine. In vivo microdialysis in NK1R-/- vs wildtype mice, locomotor activity measurement, psychostimulant treatment Journal of psychopharmacology High 19204064
2010 NK1R deletion or pharmacological blockade with L-703,606 reduces voluntary alcohol consumption and alcohol conditioned place preference in a receptor-specific, gene-dose-dependent manner; NK1R KO mice do not show escalation of alcohol intake after repeated deprivation-access cycles. Two-bottle choice alcohol consumption, conditioned place preference, NK1R KO mice, pharmacological antagonism with receptor-specificity confirmed in KO controls Psychopharmacology High 20112009
2011 SP activates NK1R and NK3R in rat mesenteric lymphatic muscle cells to stimulate phosphorylation of MLC20 (contractile pathway) and p38-MAPK/ERK1/2 (pro-inflammatory pathway); ERK1/2 inhibition decreases p-MLC20 via a PKC-dependent crosstalk between the two pathways. Cell culture pharmacological inhibition, Western blot for phosphoproteins, specific NK1R and NK3R inhibitors Microcirculation Medium 21166923
2011 NK1R-deficient mice show reduced weight gain, lower circulating leptin and insulin on high-fat diet, higher adiponectin receptor expression, reduced JNK/PKC activation in mesenteric fat, and improved glucose clearance. SP directly inhibits insulin-mediated glucose uptake in isolated rat adipocytes, establishing a role for SP/NK1R in adipose insulin signaling. NK1R KO mice on high-fat diet, glucose tolerance test, Western blot, in vitro glucose uptake in isolated adipocytes Endocrinology Medium 21467195
2013 SP promotes pancreatic cancer cell proliferation, invasion, MMP-2 expression, and perineural invasion via NK1R; NK1R antagonists block SP-induced cancer cell migration to dorsal root ganglia in a coculture model. MTT proliferation assay, Transwell Matrigel invasion assay, Western blot, neuron-tumor coculture, NK1R antagonist blockade Molecular cancer research Medium 23345604
2013 In alcohol-preferring (P) rats, elevated Tacr1 expression in the central amygdala (but not prefrontal cortex) is accompanied by elevated NK1R binding; central amygdala infusion of NK1R antagonist L822429 replicates the systemic effect on alcohol self-administration. A promoter SNP (-1372C allele) confers increased transcription factor binding (GATA-2, E2F-1) and transcription by electromobility shift and luciferase assays. Operant self-administration, central amygdala microinfusion, receptor autoradiography/binding, EMSA, luciferase reporter assay Biological psychiatry Medium 23419547
2015 SP stimulation of NK1R in human colonic epithelial NCM460 cells induces miR-221-5p expression via NF-κB and JNK pathways; miR-221-5p directly targets IL-6R mRNA (validated by luciferase reporter), and this SP/NK1R/miR-221-5p/IL-6R axis is protective in colitis models. microRNA profiling, luciferase reporter assay for IL-6R targeting, NF-κB/JNK pharmacological inhibition, in vivo colitis models (TNBS, DSS) Cellular and molecular gastroenterology and hepatology Medium 26645045
2018 MMP1 activates PAR1-expressing dorsal root ganglia neurons to release SP, which then activates NK1R on pancreatic cancer cells via SP/NK1R/ERK signaling to enhance migration, invasion, and perineural invasion; shRNA silencing of MMP1 or pharmacological blockade of PAR1 or NK1R inhibits perineural invasion. Matrigel/DRG coculture PNI model, in vivo sciatic nerve invasion model, shRNA, pharmacological antagonists, MRI imaging Theranostics Medium 29896303
2018 NK1R agonist GR73632-induced vomiting in the least shrew activates brainstem signaling through L-type Ca2+ channels and IP3R-dependent PI3K/PKCα/βII-ERK1/2 pathway; CaMKIIα, ERK1/2, Akt, and PKCα/βII are phosphorylated in brainstem after NK1R activation, and inhibitors of each step suppress vomiting. In vivo emesis assay, Western blot for phosphoproteins in brainstem, immunofluorescence, pharmacological inhibitors of LTCC, IP3R, ERK1/2, PKC, PI3K Neurochemistry international Medium 30453005
2019 SP/NK1R promotes esophageal squamous cell carcinoma cell proliferation through the NK1R/Hes1 axis: NK1R downregulation markedly reduces Hes1 expression (identified by iTRAQ proteomics), and Hes1 regulates proliferation downstream of SP/NK1R. CCK-8 and colony formation assays, iTRAQ protein spectrum analysis, Western blot, RT-qPCR, xenograft model Biochemical and biophysical research communications Medium 31109645
2021 Activation of a subset of spinal Tacr1-expressing projection neurons (expressing NK1R) evokes a full repertoire of pain-related behaviors. These neurons project to a cluster of neurons in the superior lateral parabrachial nucleus (PBN-SL) that also express Tacr1. PBN-SL Tacr1 neurons respond to sustained but not acute noxious stimuli; silencing them causes mice to ignore long-lasting noxious stimuli but does not affect acute pain. PBN-SL Tacr1 activation alone heightens nocifensive behaviors and suppresses itch. Optogenetic activation of spinal Tacr1 neurons, chemogenetic silencing of PBN-SL Tacr1 neurons, optotagging, behavioral assays for pain and itch eLife High 33591273
2021 NK1R inhibition with aprepitant suppresses NLRC4-dependent neuronal pyroptosis after intracerebral hemorrhage via NK1R/PKCδ signaling; NK1R agonist GR73632 or PKCδ agonist PMA reverses aprepitant's neuroprotective effect, and NLRC4 siRNA knockdown phenocopies aprepitant. Mouse ICH model, Western blot, immunofluorescence, intracerebroventricular injection of agonists/siRNA, neurobehavioral tests Journal of neuroinflammation Medium 35922848
2021 NK1R inhibition by aprepitant promotes hematoma clearance after ICH by increasing M2 microglial polarization via downregulation of PKC/p38MAPK/NFκB signaling; thrombin upstream increases SP, and SP activates NK1R on microglia to drive M1 polarization. Autologous blood injection ICH model, intraperitoneal and intracerebroventricular drug administration, Western blot, immunofluorescence, thrombin injection Neurotherapeutics Medium 34244927
2022 Tacr1-expressing ON cells in the rostral ventromedial medulla (RVM) are excited by substance P and exert inhibitory control over spinal pruriceptive transmission: intramedullary SP potentiates RVM ON cells and reduces pruritogen-evoked scratching; chemogenetic activation of RVM Tacr1 neurons reduces itch; optotagging confirms these are ON cells. Intramedullary SP microinjection, chemogenetic (DREADD) activation, optotagging electrophysiology, behavioral assays for itch and pain eLife High 35972457
2018 NK1R/5-HT1AR physically interact (co-immunoprecipitation) and co-localize in melanocytes and skin; SP activation of NK1R reduces 5-HT1AR expression and, when combined with 5-HT1AR antagonism, activates p-JNK signaling and inhibits p70S6K1 phosphorylation to reduce melanin production. Removal of the NK1R N-terminus prevents NK1R surface targeting and reduces the NK1R-5-HT1AR interaction. Co-immunoprecipitation, Western blot, PCR, in vitro melanin assay, in vivo mouse and zebrafish models, N-terminal deletion mutagenesis FASEB journal Medium 29430989
2020 TGFβ upregulates NK1R-Tr (truncated isoform) expression in breast cancer cells via Smad4 binding to the NK1R promoter (confirmed by ChIP and dual-luciferase reporter assay); NK1R-Tr promotes proliferation and inhibits apoptosis, and these effects are attenuated by TGFβ when NK1R is knocked down. ChIP, dual-luciferase reporter assay, Western blot, CCK-8, colony formation, flow cytometry, xenograft model Life sciences Medium 32380077
2021 SP/NK1R signaling in breast cancer (MCF-7) increases intracellular ROS and upregulates NF-κB and its pro-inflammatory targets TNF-α and IL-6; NK1R blockade by aprepitant halts cell viability partly via p53-mediated upregulation of p21. ROS assay, qRT-PCR, resazurin cell viability assay, Western blot Cell biochemistry and biophysics Low 37740877
2023 TFAP4 promotes NK1R transcription by binding to the NK1R promoter (abolished by mutation of the binding site); SP activates NK1R to engage JNK/p38 pathways to modulate tubular epithelial cell fate (growth arrest, apoptosis, profibrogenic gene expression) in chronic kidney disease. Promoter mutation assay, binding site mutagenesis, NK1R-KO mice and pharmacological antagonism in UUO model, NK1R-overexpressed HK-2 cells, Western blot Frontiers in immunology Medium 37033943

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Comparison of the phenotype of NK1R-/- mice with pharmacological blockade of the substance P (NK1 ) receptor in assays for antidepressant and anxiolytic drugs. Behavioural pharmacology 130 11742144
2018 MMP1/PAR1/SP/NK1R paracrine loop modulates early perineural invasion of pancreatic cancer cells. Theranostics 83 29896303
2013 Neurotransmitter substance P mediates pancreatic cancer perineural invasion via NK-1R in cancer cells. Molecular cancer research : MCR 83 23345604
1998 Desensitization of the neurokinin-1 receptor (NK1-R) in neurons: effects of substance P on the distribution of NK1-R, Galphaq/11, G-protein receptor kinase-2/3, and beta-arrestin-1/2. Molecular biology of the cell 79 9693383
2008 Role of spinal microglia in visceral hyperalgesia and NK1R up-regulation in a rat model of chronic stress. Gastroenterology 68 19249394
2021 A spinoparabrachial circuit defined by Tacr1 expression drives pain. eLife 65 33591273
2009 NK1 (TACR1) receptor gene 'knockout' mouse phenotype predicts genetic association with ADHD. Journal of psychopharmacology (Oxford, England) 65 19204064
2008 Substance P (SP) enhances CCL5-induced chemotaxis and intracellular signaling in human monocytes, which express the truncated neurokinin-1 receptor (NK1R). Journal of leukocyte biology 61 18835883
2005 Transient receptor potential vanilloid (TRPV-1) promotes neurogenic inflammation in the pancreas via activation of the neurokinin-1 receptor (NK-1R). Pancreas 61 15782105
2004 Interleukin-1beta upregulates functional expression of neurokinin-1 receptor (NK-1R) via NF-kappaB in astrocytes. Glia 59 15390113
2010 Neurokinin-1 receptors (NK1R:s), alcohol consumption, and alcohol reward in mice. Psychopharmacology 56 20112009
2003 IL-18 and IL-12 signal through the NF-kappa B pathway to induce NK-1R expression on T cells. Journal of immunology (Baltimore, Md. : 1950) 50 12734344
2003 Neurokinin-1 receptor (NK-1R) expression is induced in human colonic epithelial cells by proinflammatory cytokines and mediates proliferation in response to substance P. Journal of cellular physiology 43 12942538
2014 Genetic association of the tachykinin receptor 1 TACR1 gene in bipolar disorder, attention deficit hyperactivity disorder, and the alcohol dependence syndrome. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 39 24817687
2013 Tacr1 gene variation and neurokinin 1 receptor expression is associated with antagonist efficacy in genetically selected alcohol-preferring rats. Biological psychiatry 39 23419547
2011 Substance P (SP)-neurokinin-1 receptor (NK-1R) alters adipose tissue responses to high-fat diet and insulin action. Endocrinology 39 21467195
2008 Blood-brain barrier impairment with enhanced SP, NK-1R, GFAP and claudin-5 expressions in experimental cerebral toxocariasis. Parasite immunology 37 18627507
2011 Substance P activates both contractile and inflammatory pathways in lymphatics through the neurokinin receptors NK1R and NK3R. Microcirculation (New York, N.Y. : 1994) 35 21166923
2017 Upregulated expression of substance P (SP) and NK1R in eczema and SP-induced mast cell accumulation. Cell biology and toxicology 34 28154998
2017 Bidirectional relationship between alcohol intake and sensitivity to social defeat: association with Tacr1 and Avp expression. Addiction biology 33 28150369
2019 lncRNA RMRP knockdown suppress hepatocellular carcinoma biological activities via regulation miRNA-206/TACR1. Journal of cellular biochemistry 32 31579977
2007 Disruption of noradrenergic transmission and the behavioural response to a novel environment in NK1R-/- mice. The European journal of neuroscience 32 17331215
2019 Antagonism of NK-1R using aprepitant suppresses inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes. Artificial cells, nanomedicine, and biotechnology 31 31010320
2022 Aprepitant attenuates NLRC4-dependent neuronal pyroptosis via NK1R/PKCδ pathway in a mouse model of intracerebral hemorrhage. Journal of neuroinflammation 29 35922848
2021 Neurokinin-1 Receptor (NK-1R) Antagonists: Potential Targets in the Treatment of Glioblastoma Multiforme. Current medicinal chemistry 29 33441062
2012 TACR1 genotypes predict fMRI response to alcohol cues and level of alcohol dependence. Alcoholism, clinical and experimental research 29 23078527
2022 SP/NK1R system regulates carcinogenesis in prostate cancer: Shedding light on the antitumoral function of aprepitant. Biochimica et biophysica acta. Molecular cell research 28 35134443
2017 Pain in knee osteoarthritis is associated with variation in the neurokinin 1/substance P receptor (TACR1) gene. European journal of pain (London, England) 28 28493529
2021 The Effect of SP/NK1R on the Expression and Activity of Catalase and Superoxide Dismutase in Glioblastoma Cancer Cells. Biochemistry research international 26 33976938
2021 Neurokinin Receptor 1 (NK1R) Antagonist Aprepitant Enhances Hematoma Clearance by Regulating Microglial Polarization via PKC/p38MAPK/NFκB Pathway After Experimental Intracerebral Hemorrhage in Mice. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 26 34244927
2015 TACR1 gene polymorphism and sex differences in postoperative nausea and vomiting. Anaesthesia 25 26012530
2020 The NK-1R Antagonist Aprepitant Prevents LPS-Induced Oxidative Stress and Inflammation in RAW264.7 Macrophages. Drug design, development and therapy 24 32546961
2023 The SP/NK1R system promotes the proliferation of breast cancer cells through NF-κB-mediated inflammatory responses. Cell biochemistry and biophysics 22 37740877
2015 Identification of a novel substance P (SP)-neurokinin-1 receptor (NK-1R) microRNA-221-5p inflammatory network in human colonic epithelial cells. Cellular and molecular gastroenterology and hepatology 22 26645045
2010 Neurokinin-1 receptor (NK1-R) expression in the brains of SIV-infected rhesus macaques: implications for substance P in NK1-R immune cell trafficking into the CNS. The American journal of pathology 22 20671267
2001 Evidence for spatial proximity of two distinct receptor regions in the substance P (SP)*neurokinin-1 receptor (NK-1R) complex obtained by photolabeling the NK-1R with p-benzoylphenylalanine3-SP. The Journal of biological chemistry 22 11294866
2022 Neurokinin-1 Receptor (NK-1R) Antagonists as a New Strategy to Overcome Cancer Resistance. Cancers 21 35565383
2021 Chaiqin chengqi decoction ameliorates acute pancreatitis in mice via inhibition of neuron activation-mediated acinar cell SP/NK1R signaling pathways. Journal of ethnopharmacology 21 33731310
2021 Potential in vitro therapeutic effects of targeting SP/NK1R system in cervical cancer. Molecular biology reports 21 34766230
2018 Neurokinin-1 receptor (NK1R) inhibition sensitizes APL cells to anti-tumor effect of arsenic trioxide via restriction of NF-κB axis: Shedding new light on resistance to Aprepitant. The international journal of biochemistry & cell biology 21 30145367
2021 Pathogenic role of the SP/ NK1R system in GBM cells through inhibiting the thioredoxin system. Iranian journal of basic medical sciences 19 34094032
2012 Antagonism of L-type Ca(v) channels with nifedipine differentially affects performance of wildtype and NK1R-/- mice in the 5-Choice Serial Reaction-Time Task. Neuropharmacology 19 22884624
2010 Glioblastoma: synergy of growth promotion between CCL5 and NK-1R can be thwarted by blocking CCL5 with miraviroc, an FDA approved anti-HIV drug and blocking NK-1R with aprepitant, an FDA approved anti-nausea drug. Journal of clinical pharmacy and therapeutics 19 21054456
2018 Tropisetron attenuates lipopolysaccharide induced neuroinflammation by inhibiting NF-κB and SP/NK1R signaling pathway. Journal of neuroimmunology 18 29759144
2016 Pharmacologic rationale for the NK1R antagonist, aprepitant as adjunctive therapy in HIV. Journal of translational medicine 18 27230663
2015 A lack of functional NK1 receptors explains most, but not all, abnormal behaviours of NK1R-/- mice(1). Genes, brain, and behavior 18 25558794
2005 Real-time reverse transcription-PCR quantitation of substance P receptor (NK-1R) mRNA. Clinical and diagnostic laboratory immunology 18 15817763
2004 Fine mapping of the 2p11 dyslexia locus and exclusion of TACR1 as a candidate gene. Human genetics 18 15007729
2022 Dramatic Effect of Botulinum Toxin Type A on Hypertrophic Scar: A Promising Therapeutic Drug and Its Mechanism Through the SP-NK1R Pathway in Cutaneous Neurogenic Inflammation. Frontiers in medicine 17 35308522
2020 Radiochemical Synthesis and Evaluation of Novel Radioconjugates of Neurokinin 1 Receptor Antagonist Aprepitant Dedicated for NK1R-Positive Tumors. Molecules (Basel, Switzerland) 17 32824729
2019 SP promotes cell proliferation in esophageal squamous cell carcinoma through the NK1R/Hes1 axis. Biochemical and biophysical research communications 17 31109645
2018 Intracellular emetic signaling cascades by which the selective neurokinin type 1 receptor (NK1R) agonist GR73632 evokes vomiting in the least shrew (Cryptotis parva). Neurochemistry international 17 30453005
2012 Diminished pheromone-induced sexual behavior in neurokinin-1 receptor deficient (TACR1(-/-)) mice. Genes, brain, and behavior 17 22471406
2009 Association and linkage analysis of candidate genes GRP, GRPR, CRHR1, and TACR1 in panic disorder. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 17 18452185
1996 Recognition of neurokinin 1 receptor (NK1-R): an antibody to a peptide sequence from the third extracellular region binds to brain NK1-R. Journal of neuroimmunology 17 8707930
2021 Carbohydrate-Based NK1R Antagonists with Broad-Spectrum Anticancer Activity. Journal of medicinal chemistry 16 34236855
2014 Expression of different neurokinin-1 receptor (NK1R) isoforms in glioblastoma multiforme: potential implications for targeted therapy. Cancer biotherapy & radiopharmaceuticals 16 24552486
2013 The influence of test experience and NK1 receptor antagonists on the performance of NK1R-/- and wild type mice in the 5-Choice Serial Reaction-Time Task. Journal of psychopharmacology (Oxford, England) 16 23845920
2009 A paradoxical protective role for the proinflammatory peptide substance P receptor (NK1R) in acute hyperoxic lung injury. American journal of physiology. Lung cellular and molecular physiology 16 19633070
2022 The Potential In Vitro Inhibitory Effects of Neurokinin-1 Receptor (NK-1R) Antagonist, Aprepitant, in Osteosarcoma Cell Migration and Metastasis. BioMed research international 15 36177059
2021 Significance of the Overexpression of Substance P and Its Receptor NK-1R in Head and Neck Carcinogenesis: A Systematic Review and Meta-Analysis. Cancers 15 33802704
1997 A monoclonal antibody to the ligand-binding domain of the neurokinin 1 receptor (NK1-R) for the neuropeptide substance P. Journal of neuroimmunology 15 9184627
2022 Novel NK1R-Targeted 68Ga-/177Lu-Radioconjugates with Potential Application against Glioblastoma Multiforme: Preliminary Exploration of Structure-Activity Relationships. International journal of molecular sciences 14 35163139
2019 NK1-r Antagonist Treatment Comparable to Decompressive Craniectomy in Reducing Intracranial Pressure Following Stroke. Frontiers in neuroscience 14 31333402
2017 Up-regulated expression of substance P in CD8+ T cells and NK1R on monocytes of atopic dermatitis. Journal of translational medicine 14 28460633
2003 Pregnancy-induced changes in substance P and neurokinin 1 receptor (NK1-R) expression in the rat uterus. Reproduction (Cambridge, England) 14 14525527
2022 Inhibition of itch by neurokinin 1 receptor (Tacr1) -expressing ON cells in the rostral ventromedial medulla in mice. eLife 13 35972457
2021 The SP/NK1R System-Mediated ROS Generation in GBM Cells through Inhibiting Glutaredoxin Protein. Neurology research international 13 34917417
2016 Perseveration by NK1R-/- ('knockout') mice is blunted by doses of methylphenidate that affect neither other aspects of their cognitive performance nor the behaviour of wild-type mice in the 5-Choice Continuous Performance Test. Journal of psychopharmacology (Oxford, England) 13 27097734
2003 Relationship between overexpression of NK-1R, NK-2R and intestinal mucosal damage in acute necrotizing pancreatitis. World journal of gastroenterology 13 12508374
2023 Novel trajectories of the NK1R antagonist aprepitant in rotenone-induced Parkinsonism-like symptoms in rats: Involvement of ERK5/KLF4/p62/Nrf2 signaling axis. Chemico-biological interactions 12 37224993
2015 Differences in the performance of NK1R-/- ('knockout') and wildtype mice in the 5‑Choice Continuous Performance Test. Behavioural brain research 12 26522842
2006 LIF upregulates expression of NK-1R in NHBE cells. Mediators of inflammation 12 17392578
2014 Tachykinin peptide, substance P, and its receptor NK-1R play an important role in alimentary tract mucosal inflammation during cytotoxic therapy. Digestive diseases and sciences 11 24981415
2006 Nuclear localization of SP, CGRP, and NK1R in a subpopulation of dorsal root ganglia subpopulation cells in rats. Cellular and molecular neurobiology 11 16763782
2025 A Silk Fibroin Nanoparticle Hydrogel Loaded With NK1R Antagonist Has Synergistic Anti-Inflammatory and Reparative Effects on Dry Eye Disease. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 10 39985258
2023 The In Vitro Pro-inflammatory Functions of the SP/NK1R System in Prostate Cancer: a Focus on Nuclear Factor-Kappa B (NF-κB) and Its Pro-inflammatory Target Genes. Applied biochemistry and biotechnology 10 37093533
2020 Inhibition of NK1R attenuates LPS-induced microglial inflammation and consequent death of PC12 cells. Brain research bulletin 10 32540418
2020 In Vivo, In Vitro and In Silico Studies of the Hybrid Compound AA3266, an Opioid Agonist/NK1R Antagonist with Selective Cytotoxicity. International journal of molecular sciences 10 33086743
2018 Synthesis and Evaluation of a Novel 64Cu- and 67Ga-Labeled Neurokinin 1 Receptor Antagonist for in Vivo Targeting of NK1R-Positive Tumor Xenografts. Bioconjugate chemistry 10 29466853
2016 A comparative QSAR analysis and molecular docking studies of phenyl piperidine derivatives as potent dual NK1R antagonists/serotonin transporter (SERT) inhibitors. Computational biology and chemistry 10 28043073
2004 Localization of neurokinin 1 receptor (NK1R) immunoreactivity in rat esophagus. The Journal of comparative neurology 10 15334646
2024 The effect of SP/NK1R on expression and activity of glutaredoxin and thioredoxin proteins in prostate cancer cells. Naunyn-Schmiedeberg's archives of pharmacology 9 38334824
2022 Upregulated expression of substance P and NK1R in blood monocytes and B cells of patients with allergic rhinitis and asthma. Clinical and experimental immunology 9 36001730
2019 Excitation of Cortical nNOS/NK1R Neurons by Hypocretin 1 is Independent of Sleep Homeostasis. Cerebral cortex (New York, N.Y. : 1991) 9 29462275
2016 Generation of a NK1R-CreER knockin mouse strain to study cells involved in Neurokinin 1 Receptor signaling. Genesis (New York, N.Y. : 2000) 9 27712014
2015 Prenatal nicotinic exposure upregulates pulmonary C-fiber NK1R expression to prolong pulmonary C-fiber-mediated apneic response. Toxicology and applied pharmacology 9 26524655
2005 Expression and localization of NK(1)R, substance P and CGRP are altered in dorsal root ganglia neurons of spontaneously hypertensive rats (SHR). Brain research. Molecular brain research 9 15869822
2023 Targeting NK-1R attenuates renal fibrosis via modulating inflammatory responses and cell fate in chronic kidney disease. Frontiers in immunology 8 37033943
2020 TGFβ regulates NK1R-Tr to affect the proliferation and apoptosis of breast cancer cells. Life sciences 8 32380077
2020 The Hsa_circ_0091579/miR-940/TACR1 Axis Regulates the Development of Hepatocellular Carcinoma. Cancer management and research 8 33061603
2018 NK1R/5-HT1AR interaction is related to the regulation of melanogenesis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 8 29430989
2015 The rs3771863 single nucleotide polymorphism of the TACR1 gene is associated to a lower risk of sicca syndrome in fibromyalgia patients. Clinical and experimental rheumatology 8 25786041
2011 NCAM1, TACR1 and NOS genes and temperament: a study on suicide attempters and controls. Neuropsychobiology 8 21577011
2005 Alleles on rat chromosome 4 (D4Got41-Fabp1/Tacr1) regulate subphenotypes of obesity. Obesity research 8 15833945
2024 Suppressing the Substance P-NK1R Signalling Protects Mice against Sepsis-Associated Acute Inflammatory Injury and Ferroptosis in the Liver and Lungs. Antioxidants (Basel, Switzerland) 7 38539834
2014 Neurokinin-1 receptor expression and antagonism by the NK-1R antagonist maropitant in canine melanoma cell lines and primary tumour tissues. Veterinary and comparative oncology 7 24751104
2009 Substance P and NK-1R expression in oral precancerous epithelium. Oncology reports 7 19885583
2023 Potential therapeutic effect of NK1R antagonist in diabetic non-healing wound and depression. Frontiers in endocrinology 6 36686487
2016 The NK1R-/- mouse phenotype suggests that small body size, with a sex- and diet-dependent excess in body mass and fat, are physical biomarkers for a human endophenotype with vulnerability to attention deficit hyperactivity disorder. Journal of psychopharmacology (Oxford, England) 6 27462087

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