Nomenclature: NK1 receptor

Family: Tachykinin receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 407 2p12 TACR1 tachykinin receptor 1 38,115
Mouse 7 407 6 D1 Tacr1 tachykinin receptor 1 114
Rat 7 407 4q34 Tacr1 tachykinin receptor 1 51
Previous and Unofficial Names
Names References
SPR 115
NK1-R
Substance P receptor
Substance P
TAC1R
NK1R
NKIR
NK-1 receptor
NK-1R
Tachykinin 1 receptor
Tachykinin 1 receptor (substance P receptor neurokinin 1 receptor)
Tachykinin 1 receptor (substance P receptor neurokinin 1 receptor) see also D4Mgh17 D4Wox19 and D4Mit23
neurokinin 1 receptor
substance-P receptor
tachykinin receptor 1
NK1 receptor
neurokinin receptor 1
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
neurokinin A {Sp: Human, Mouse, Rat}
neurokinin B {Sp: Human, Mouse, Rat, Pig}
substance P {Sp: Human, Mouse, Rat}
Comments: substance P is the highest potency endogenous agonist
Rank order of potency (Human)
substance P (TAC1, P20366) > neurokinin A (TAC1, P20366) > neurokinin B (TAC3, Q9UHF0)
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]BH-[Sar9,Met(O2)11]SP Rn Full agonist 9.0 pKd 120
pKd 9.0 (Kd 1x10-9 M) [120]
hemokinin 1 {Sp: Mouse} Hs Full agonist 9.8 – 11.7 pKi 10
pKi 9.8 – 11.7 [10]
substance P {Sp: Human, Mouse, Rat} Hs Full agonist 8.5 – 10.3 pKi 10-11
pKi 8.5 – 10.3 [10-11]
septide Hs Full agonist 7.0 – 9.3 pKi 10,50
pKi 7.0 – 9.3 [10,50]
neurokinin A {Sp: Human, Mouse, Rat} Hs Full agonist 6.2 – 9.3 pKi 10,39,50,107
pKi 6.2 – 9.3 [10,39,50,107]
neurokinin B {Sp: Human, Mouse, Rat, Pig} Hs Full agonist 6.1 – 6.4 pKi 107
pKi 6.1 – 6.4 [107]
[Sar9,Met(O2)11]SP Hs Full agonist 9.7 – 9.9 pIC50 117
pIC50 9.7 – 9.9 [117]
physalaemin Hs Full agonist 9.1 – 9.2 pIC50 117
pIC50 9.1 – 9.2 [117]
eledoisin Hs Full agonist 8.6 pIC50 117
pIC50 8.6 [117]
phyllomedusin Hs Full agonist 8.3 – 8.5 pIC50 117
pIC50 8.3 – 8.5 [117]
substance P-(4-11) Hs Full agonist 7.7 – 8.0 pIC50 117
pIC50 7.7 – 8.0 [117]
neuropeptide-α Hs Full agonist 7.5 – 7.7 pIC50 117
pIC50 7.5 – 7.7 [117]
substance P-OMe Hs Full agonist 7.4 – 7.5 pIC50 117
pIC50 7.4 – 7.5 [117]
kassinin Hs Full agonist 6.6 – 7.1 pIC50 117
pIC50 6.6 – 7.1 [117]
neuropeptide K {Sp: Human, Rat} Hs Full agonist 6.4 – 6.5 pIC50 117
pIC50 6.4 – 6.5 [117]
substance P-(6-11) Hs Full agonist 6.3 – 6.5 pIC50 117
pIC50 6.3 – 6.5 [117]
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
spantide II Cp Antagonist 7.0 – 8.1 pA2 34,57
pA2 7.0 – 8.1 [34,57]
spantide I Cp Antagonist 7.0 – 7.1 pA2 34,57
pA2 7.0 – 7.1 [34,57]
aprepitant Hs Antagonist 10.7 pKi 49
pKi 10.7 [49]
vofopitant Hs Antagonist 10.6 pKi 36
pKi 10.6 [36]
T2328 Hs Antagonist 10.1 pKi 127
pKi 10.1 (Ki 8x10-11 M) [127]
LY303870 Hs Antagonist 9.8 – 10.0 pKi 41
pKi 9.8 – 10.0 (Ki 1.5x10-10 – 1x10-10 M) [41]
ezlopitant Hs Antagonist 9.7 pKi 122
pKi 9.7 (Ki 2x10-10 M) [122]
CP 99994 Hs Antagonist 9.3 – 9.7 pKi 5,107
pKi 9.3 – 9.7 [5,107]
casopitant Hs Antagonist 9.4 pKi 55
pKi 9.4 [55]
vestipitant Hs Antagonist 9.37 pKi 14
pKi 9.37 [14]
R116031 Hs Antagonist 9.35 pKi 74
pKi 9.35 (Ki 4.5x10-10 M) [74]
rolapitant Hs Antagonist 9.18 pKi 30
pKi 9.18 (Ki 6.6x10-10 M) [30]
FK888 Hs Antagonist 9.1 pKi 58
pKi 9.1 (Ki 8x10-10 M) [58]
netupitant Hs Antagonist 9.02 pKi 54
pKi 9.02 (Ki 9.5x10-10 M) [54]
befetupitant Hs Antagonist 9.0 pKi 54
pKi 9.0 (Ki 1x10-9 M) [54]
SCH 206272 Hs Antagonist 8.3 – 8.9 pKi 5
pKi 8.3 – 8.9 [5]
R-486 Hs Antagonist 6.5 – 6.6 pKi 5
pKi 6.5 – 6.6 [5]
saredutant Hs Antagonist 6.1 – 6.6 pKi 5,107
pKi 6.1 – 6.6 [5,107]
osanetant Hs Antagonist 6.0 – 6.6 pKi 5
pKi 6.0 – 6.6 [5]
spantide I Rn Antagonist 5.6 pEC50 57
pEC50 5.6 Inhibition of histamine release from peritoneal mast cells [57]
spantide II Rn Antagonist 5.5 pEC50 57
pEC50 5.5 Inhibition of histamine release from peritoneal mast cells. [57]
ZD6021 Hs Antagonist 9.9 pIC50 101
pIC50 9.9 [101]
LY303870 Hs Antagonist 9.82 pIC50 55
pIC50 9.82 (IC50 1.5x10-10 M) [55]
nolpitantium Hs Antagonist 8.9 – 9.0 pIC50 117
pIC50 8.9 – 9.0 [117]
L-703,606 Hs Antagonist 8.2 – 8.4 pIC50 117
pIC50 8.2 – 8.4 [117]
spantide I Oc Antagonist 8.28 pIC50 34
pIC50 8.28 (IC50 5.2x10-9 M) Measuring iInhibition of contraction of the rabbit iris sphincter. [34]
spantide II Oc Antagonist 8.22 pIC50 34
pIC50 8.22 (IC50 6x10-9 M) Measuring iInhibition of contraction of the rabbit iris sphincter. [34]
FK 224 Hs Antagonist 7.5 – 8.3 pIC50 76
pIC50 7.5 – 8.3 [76]
RP67580 Hs Antagonist 7.7 pIC50 35
pIC50 7.7 [35]
spantide I Rn Antagonist 5.7 pIC50 129
pIC50 5.7 (IC50 2x10-6 M) [129]
osanetant Hs Antagonist 5.6 pIC50 9
pIC50 5.6 [9]
[18F]SPA-RQ Hs Antagonist - - 21
[21]
View species-specific antagonist tables
Antagonist Comments
[116] and [60] both provide evidence indicating that spantide I is an antagonist of the human NK1 receptor.
Primary Transduction Mechanisms
Transducer Effector/Response
Gs family
Gq/G11 family
Adenylate cyclase stimulation
Phospholipase C stimulation
References:  47,66,70,80,113
Tissue Distribution
Human monocytes and macrophages.
Species:  Human
Technique:  RT-PCR.
References:  53
Human arterial (umbilical) endothelium.
Species:  Human
Technique:  Autoradiography.
References:  46
Adipose tissue, prostate, pituitary.
Species:  Human
Technique:  in situ hybridisation.
References:  15
Hematopoietic Progenitors (CD34+).
Species:  Human
Technique:  RT-PCR.
References:  52
Neuroblastoma.
Species:  Human
Technique:  Western blot.
References:  77
Bone marrow stroma.
Species:  Human
Technique:  Radioligand binding.
References:  92
Intestinal epithelial cells.
Species:  Human
Technique:  Autoradiography.
References:  44
Brain cells.
Species:  Human
Technique:  RT-PCR.
References:  71
Colonic epithelial cells.
Species:  Human
Technique:  Western blot.
References:  40
T-Helper cells.
Species:  Human
Technique:  Antagonist effect.
References:  26
Striatum > cerebral cortex, hippocampus, amygdala > thalamus, cerebellum.
Species:  Human
Technique:  in situ hybridisation.
References:  15
Striatum > cerebral cortex.
Species:  Human
Technique:  Autoradiography.
References:  15
Brain; pial surface, mid to upper cortical layers.
Species:  Human
Technique:  Immunohistochemistry.
References:  119
Prefrontal and visual cortex; thin band at the cortical surface and dots of localised on small non-pyramidal cells and in the neuropil (layers I-III).
Species:  Human
Technique:  Immunohistochemistry.
References:  118
Breast cancer cells.
Species:  Human
Technique:  Western blot.
References:  18,87,95
Bone marrow fibroblasts.
Species:  Human
Technique:  Immunocytochemistry.
References:  19
Mouse ileum; interstitial cells of Cajal at the deep muscular plexus, myoid cells of the villi.
Species:  Mouse
Technique:  Immunohistochemistry.
References:  125
Uterus.
Species:  Mouse
Technique:  Autoradiography.
References:  7
Pancreatic acini.
Species:  Rat
Technique:  immunocytochemistry.
References:  13
Gastrointestinal tract.
Species:  Rat
Technique:  Immunohistochemistry.
References:  45
Brainstem auditory nuclei; cochlear nucleus, lateral superior olive, the medial nucleus of the trapezoid body, and inferior colliculus.
Species:  Rat
Technique:  Immunohistochemistry.
References:  48
Superior cervical ganglia.
Species:  Rat
Technique:  Quantitative autoradiography of spontaneously hypertensive rats.
References:  108
Kidney.
Species:  Rat
Technique:  Autoradiography.
References:  20
Tissue Distribution Comments
The NK1 receptor is widely distributed but is increased in malignant cells and appears to facilitate HIV-1 infection. Understanding of the distribution of NK1 subsets (long-form and truncated) on different cancer subsets and the effects on immune cell function are essential for efficient targeting of cancer cells.

NK1 also induces the polarization of T-helper subsets of cells, indicating that specific antagonists could prevent infection and inflammation.
Expression Datasets

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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
Measurement of cAMP accumulation in COS-7 cells transfected with the human NK1.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Stimulation of cAMP accumulation.
References:  70
Measurement of IP levels in COS-7 cells transfected with the human NK1 receptor.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Stimulation of IP turnover.
References:  70
Measurement of interleukin-6 secretion from human astrocytoma cell line U 373 MG endogenously expressing the NK1 receptor.
Species:  Human
Tissue:  U 373 MG cells.
Response measured:  Promotion of secretion of interleukin-6.
References:  42
Measurement of calcium transients in murine colonic myocytes following parallel stimulation of NK1 and NK2.
Species:  Mouse
Tissue:  Colonic myocytes.
Response measured:  Low agonist concentration increases Ca2+ transients. Higher agonist concentration increases basal Ca2+ and inhibits Ca2+ transients.
References:  8
Measurement of IP turnover in rat anterior pituitary membrane cells endogenously expressing NK1.
Species:  Rat
Tissue:  Anterior pituitary membrane.
Response measured:  Stimulation of IP turnover.
References:  72
Measurement of activation of NF-κB in human lung epithelial cells endogenously expressing the NK1 receptor.
Species:  Human
Tissue:  Lung epithelial cells.
Response measured:  NF-κB activation.
References:  128
Induction of tracheal smooth muscle contraction
Species:  Pig
Tissue:  Smooth muscle.
Response measured:  Tracheal contraction.
References:  110
Physiological Functions
Induction of pressor and tachycardic effects.
Species:  Rat
Tissue: 
References:  124
Release of nitric oxide.
Species:  Human
Tissue:  Endothelium of arterial vessels.
References:  86,100
Measurement of saliva production; saliva accumulated.
Species:  Rat
Tissue:  Submandibular glands.
References:  59
Measurement of saliva production; saliva not accumulated.
Species:  Mouse
Tissue:  Submandibular glands
References:  59
Exogenous activation induced reinstatement of cocaine-seeking behaviour, but endogenous activity at these receptors was not involved in mediating the priming effects of cocaine on reinstatement of drug-seeking behavior.
Species:  Rat
Tissue:  in vivo
References:  90
Endogenous activity attenuated morhphine-induced locomotor activity and increased heroin self-administration (but had no effect on cocaine-induced locomotor activity or self-administration).
Species:  Rat
Tissue:  in vivo
References:  89
Ganglionic NK1 receptors mediate renal nerve, heart rate and pressor response to Substance P.
Species:  Rat
Tissue:  In vivo (sympathetic ganglia).
References:  108
Initiates micturation reflex.
Species:  Rat
Tissue:  In vivo
References:  67-68,84
Stimulates licking, biting and scratching response.
Species:  Mouse
Tissue:  In vivo
References:  104-106
Mediates plasma extravasation in footpad.
Species:  Rat
Tissue:  In vivo.
References:  4
5-Hydroxytryptamine-induced tracheal contraction includes a cholinergic mechanism that requires the presence of the tachykinin NK(1) receptor.
Species:  Mouse
Tissue:  Trachea
References:  29
Stimulation of behaviour in resident-intruder and forced swim test resembling that seen with the clinically used antidepressent fluoxetine.
Species:  Mouse
Tissue:  In vivo
References:  102
Regulation of severity of acute pancreatitis and pancreatitis-associated lung injury.
Species:  Mouse
Tissue:  In vivo
References:  67
Mediation of substance P-induced edema formation.
Species:  Mouse
Tissue:  In vivo
References:  16
Patients with moderate to severe major depression, robust antidepressant effects were consistently observed upon treatment with and NK1 antagonist.
Species:  Human
Tissue:  In vivo
References:  65
Modulation of nociceptive behaviour induced by intrathecal injection of histamine.
Species:  Mouse
Tissue:  In vivo
References:  130
Intrathecal administration of an NK1 receptor antagonist blocks the colorectal-distension-induced hyperalgesia for both noxious and innocuous stimuli.
Species:  Rat
Tissue:  In vivo.
References:  37
NK1 receptor is required in antigen-induced cystitis.
Species:  Mouse
Tissue:  In vivo
References:  103
Activation of the NK1 receptor modulates vascular tone and permeability in the inflamed joints in knockout mice studies.
Species:  Mouse
Tissue:  In vivo
References:  62
NK1 receptor blockade stimulates the proliferation of neurons in the dentate gyrus suggesting that NK1R blockade may generate anti-depressant-like effects.
Species:  Mouse
Tissue:  In vivo
References:  75
Grooming is induced by the NK1 agonist administered into the substantia nigra.
Species:  Rat
Tissue:  In vivo.
References:  112
Modulation of spontaneous and drug-induced locomotor activity.
Species:  Rat
Tissue:  In vivo.
References:  111
Control of presynaptic dopamine release.
Species:  Rat
Tissue:  In vivo.
References:  43,121
Analgesic effects are induced by NK1 receptor agonists administered to either the ventral tegmental area or nucleus accumbens septi.
Species:  Human
Tissue:  In vivo.
References:  3
Mediates the effect of intravenous tachykinins on vascular permeability in the rat lower urinary tract, through a histamine-independent mechanism.
Species:  Human
Tissue:  Rat lower urinary tract.
References:  1
NK1 receptors are involved in mediating PNV-induced scratching.
Species:  Mouse
Tissue:  In vivo
References:  24
Aprepitant does not reduce the incidence of post-ERCP (endoscopic retrograde cholangiopancreatography) pancreatitis in humans.
Species:  Human
Tissue:  In vivo.
References:  109
NK1 receptor antagonist N-acetyl-L-tryptophan (NAT) improves outcome in female Sprague Dawley rats following diffuse traumatic brain injury.
Species:  Rat
Tissue:  In vivo.
References:  23
NK1 receptor antagonist L-732,138 co-administration attenuates opioid withdrawal-mediated spinal microglia and astrocyte activation in rats.
Species:  Rat
Tissue:  In vivo.
References:  123
Blockade of NK1 receptors with the antagonists L-733,060 and RP-67580 alleviates renal functional and tissue injury in the absence of alteration in blood pressure in DOCA-salt-hypertensive mice.
Species:  Mouse
Tissue:  In vivo.
References:  126
Physiological Consequences of Altering Gene Expression
NK1 knockout mice display increased numbers of mast cells in the bladder when compared with the wild type.
Species:  Mouse
Tissue:  Bladder.
Technique:  Gene knockout.
References:  82
Disruption of noradrenaline regulation is observed in NK1 knockout mice.
Species:  Human
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  33
NK1 knockout mice did not display stress-triggered premature induction of catagen and hair follicle apoptosis, compared to wild type.
Species:  Mouse
Tissue:  Hair follicle.
Technique:  Gene knockout.
References:  6
In an intense inflammatory model produced by intra-plantar Mycobacterium tuberculosus, substantial reductions in footpad swelling, histological outcome and mechanical hyperalgesia are observed from early time points in mice lacking the neurokin-1 receptor compared with wild-type controls.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  63
NK1 knockout mice display decreased Phoneutria nigriventer spider venom and substance P-induced oedema formation when compared to the wild-type. NK1 knockout mice display decreased Phoneutria nigriventer spider venom-induced scratching when compared to the wild-type.
Species:  Mouse
Tissue: 
Technique:  Gene tagging in embryonic stem cells
References:  24
In resident-intruder and forced swim tests, NK1 knockout mice display behaviour resembling that seen with the clinically used antidepressent fluoxetine.
Species:  Mouse
Tissue: 
Technique:  Gene tagging in embryonic stem cells
References:  102
NK1 knockout mice shown increased neurogenesis and levels of brain-derived neurotrophic factor in the hippocampus when compared to the wild-type.
Species:  Mouse
Tissue: 
Technique:  Gene tagging in embryonic stem cells
References:  75
Compared to wild type, NK1 knockout mice displayed molecular modifications of signaling pathways involved in the pathophysiology of depression and antidepressant mechanism, such as up-regulation of Ca(2+)-independent enzymatic activity in the prefrontal/frontal cortex, hippocampus and striatum.
Species:  Mouse
Tissue: 
Technique:  Gene tagging in embryonic stem cells
References:  78
NK1 knockout mice display altered nociception, analgesia and aggression compared to the wild-type
Species:  Mouse
Tissue: 
Technique:  Gene tagging in embryonic stem cells
References:  28
The severity of induced pancreatitis in mice lacking the NK1 receptor is decreased compared to the wild=type.
Species:  Mouse
Tissue: 
Technique:  Gene tagging in embryonic stem cells
References:  12
NK1 knockout mice displayed decreased induced neutrophil accumulation when treated with interleukin-1β, compared to the wild -type.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells
References:  2
NK1 knockout mice displayed decreased induced neutrophil accumulation when treated with interleukin-1β, compared to the wild -type.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells
References:  2
NK1 knockout mice display an abnormal granulomatuous response in Shistosomiasis Mansoni.
Species:  Mouse
Tissue: 
Technique:  Gene knockout.
References:  12
NK1 knockout mice are protected from the secretory and inflammatory changes as well as from epithelial cell damage induced by toxin A in the intestine.
Species:  Mouse
Tissue:  Intestine.
Technique:  Gene knock-outs.
References:  17
Substance P causes significant acute plasma extravasation in wild type but not NK1 knockout mice. Complete Freund's adjuvant induced a significant decrease in intravascular volume at early time points in wild type but not NK1 knockout mice. Substance P injection into complete Freund's adjuvant-pretreated joints causes a significant enhancement of plasma extravasation and knee swelling in wild type but not NKNK1 knockout mice.
Species:  Mouse
Tissue: 
Technique:  Gene knockout.
References:  62
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6
MGI:98475  MP:0002735 abnormal chemical nociception PMID: 9537323 
Tacr1tm1Nge Tacr1tm1Nge/Tacr1tm1Nge
involves: 129S4/SvJae
MGI:98475  MP:0001800 abnormal humoral immune response PMID: 8781237 
Tacr1tm1Nge Tacr1tm1Nge/Tacr1tm1Nge
involves: 129S4/SvJae * C57BL
MGI:98475  MP:0002423 abnormal mast cell physiology PMID: 12867261 
Tacr1tm1Nge Tacr1tm1Nge/Tacr1tm1Nge
involves: 129S4/SvJae
MGI:98475  MP:0002272 abnormal nervous system electrophysiology PMID: 11465604 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129 * C57BL/6
MGI:98475  MP:0003633 abnormal nervous system physiology PMID: 10954331 
Tacr1tm1Rhn Tacr1tm1Rhn/Tacr1tm1Rhn
129S/SvEv-Tacr1
MGI:98475  MP:0004811 abnormal neuron physiology PMID: 11172050 
Tacr1tm1Rhn Tacr1tm1Rhn/Tacr1tm1Rhn
129S/SvEv-Tacr1
MGI:98475  MP:0002736 abnormal nociception after inflammation PMID: 10718319 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6
MGI:98475  MP:0001970 abnormal pain threshold PMID: 9537323 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd
MGI:98475  MP:0001970 abnormal pain threshold PMID: 11433347 
Tacr1tm1Rhn Tacr1tm1Rhn/Tacr1tm1Rhn
129S/SvEv-Tacr1
MGI:98475  MP:0008872 abnormal physiological response to xenobiotic PMID: 11172050 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6
MGI:98475  MP:0002327 abnormal respiratory function PMID: 12492418 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6
MGI:98475  MP:0002281 abnormal respiratory mucosa goblet cell morphology PMID: 15208590 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6 * MF1
MGI:98475  MP:0003663 abnormal thermosensation PMID: 15964684 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6
MGI:98475  MP:0001968 abnormal touch/ nociception PMID: 9537323 
Tacr1tm1Rhn Tacr1tm1Rhn/Tacr1tm1Rhn
129S/SvEv-Tacr1
MGI:98475  MP:0001529 abnormal vocalization PMID: 11172050 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6
MGI:98475  MP:0005656 decreased aggression PMID: 9537323 
Tacr1tm1Rhn Tacr1tm1Rhn/Tacr1tm1Rhn
129S/SvEv-Tacr1
MGI:98475  MP:0001364 decreased anxiety-related response PMID: 11172050 
Tacr1tm1Rhn Tacr1tm1Rhn/Tacr1tm1Rhn
129S/SvEv-Tacr1
MGI:98475  MP:0002665 decreased circulating corticosterone level PMID: 11172050 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6
MGI:98475  MP:0001876 decreased inflammatory response PMID: 9537323 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6
MGI:98475  MP:0003481 decreased nerve fiber response intensity PMID: 9537323 
Tacr1tm1Nge Tacr1tm1Nge/Tacr1tm1Nge
involves: 129S4/SvJae * C57BL
MGI:98475  MP:0003071 decreased vascular permeability PMID: 12867261 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6 * MF1
MGI:98475  MP:0001399 hyperactivity PMID: 15814105 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6
MGI:98475  MP:0005407 hyperalgesia PMID: 14625445 
Tacr1tm1Rhn Tacr1tm1Rhn/Tacr1tm1Rhn
129S/SvEv-Tacr1
MGI:98475  MP:0005498 hyporesponsive to tactile stimuli PMID: 10718319 
Tacr1tm1Rhn Tacr1tm1Rhn/Tacr1tm1Rhn
129S/SvEv-Tacr1
MGI:98475  MP:0009747 impaired behavioral response to xenobiotic PMID: 11172050 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6
MGI:98475  MP:0001952 increased airway responsiveness PMID: 15208590 
Tacr1tm1Rhn Tacr1tm1Rhn/Tacr1tm1Rhn
129S/SvEv-Tacr1
MGI:98475  MP:0005533 increased body temperature PMID: 11172050 
Tacr1tm1Rhn Tacr1tm1Rhn/Tacr1tm1Rhn
129S/SvEv-Tacr1
MGI:98475  MP:0008531 increased chemical nociceptive threshold PMID: 10718319 
Tacr1tm1Sph Tacr1tm1Sph/Tacr1tm1Sph
involves: 129P2/OlaHsd * C57BL/6
MGI:98475  MP:0002933 joint inflammation PMID: 14625445 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Wound/Tissue adhesion
References:  22,61,98-99
Mutations not determined
Disease:  Breast cancer
References:  56,73,79,81,85,87,91,96-97
Mutations not determined
Disease:  Colitis induced transformation
References:  40,83
Mutations not determined
Disease:  Colitis
References:  27,32,64,69
Mutations not determined
Disease:  Myelofibrosis
References:  19,93-94
Mutations not determined
Disease:  Colitis fibrosis
References:  64
Mutations not determined
Clinically-Relevant Mutations and Pathophysiology Comments
The truncated form of neurokinin-1 receptor has been linked to breast cancer. It appears that this short form of neuroninin-1 can induce the induction of the TAC1 gene, resulting in cell autonomous proliferation. It is unclear if the truncated neurokin 1 receptor is involved in the transition of low invasive cancer cells to highly aggressive malignancy. Insights into this question was provided in studies with colitis patients. As the subjects transitioned to malignant transformation, the truncated neurokinin-1 receptor was increased. These studies strongly suggest that targeting the neurokinin-1 receptor could prevent inflammation-induced transformation.
General Comments
In rats subjected to chronic and acute stress or pain, expression of the NK1 receptor in the hippocampus is down-regulated [31]. NK1 expression in pancreatic acinar cells in mice is increased during secratogogue-induced experimental pancreatitis [12]. Respiratory syncytial virus upregulates expression of NK1 in rat lungs [88]. Ablation of NK1-expressing rat spinal neurons with the selective cytotoxin substance P-saporin results in an apparently permanent reduction of thermal hyperalgesia and mechanical allodynia associated with persistent neuropathic and inflammatory pain states [82]. Chronic stimulation of NK1 induces ubiquitination of the receptor, which mediates its degradation and down-regulation [25].
Available Assays
DiscoveRx PathHunter® C2C12 TACR1 β-Arrestin Cell Line (Cat no. 93-0344C7)
PathHunter® CHO-K1 TACR1 β-Arrestin Cell Line (Cat no. 93-0344C2)
PathHunter® eXpress TACR1 CHO-K1 β-Arrestin GPCR Assay (Cat no. 93-0344E2CP0M)
more info

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Steven D. Douglas, Susan E. Leeman, Jeffrey Barrett, Erin Dombrowsky, Christa Y. Heyward, Pranela Remeshwar.
Tachykinin receptors: NK1 receptor. Last modified on 19/05/2014. Accessed on 01/09/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=360.

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