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NK1 receptor

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Target id: 360

Nomenclature: NK1 receptor

Family: Tachykinin receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 407 2p12 TACR1 tachykinin receptor 1 43,126
Mouse 7 407 6 C3 Tacr1 tachykinin receptor 1 125
Rat 7 407 4q34 Tacr1 tachykinin receptor 1 58
Previous and Unofficial Names Click here for help
SPR [126] | Substance P receptor | NK1R | TAC1R | neurokinin receptor 1 | NK1 receptor
Database Links Click here for help
Specialist databases
GPCRdb nk1r_human (Hs), nk1r_mouse (Mm), nk1r_rat (Rn)
Other databases
Alphafold P25103 (Hs), P30548 (Mm), P14600 (Rn)
ChEMBL Target CHEMBL249 (Hs), CHEMBL2668 (Mm), CHEMBL4027 (Rn)
DrugBank Target P25103 (Hs)
Ensembl Gene ENSG00000115353 (Hs), ENSMUSG00000030043 (Mm), ENSRNOG00000005853 (Rn)
Entrez Gene 6869 (Hs), 21336 (Mm), 24807 (Rn)
Human Protein Atlas ENSG00000115353 (Hs)
KEGG Gene hsa:6869 (Hs), mmu:21336 (Mm), rno:24807 (Rn)
OMIM 162323 (Hs)
Pharos P25103 (Hs)
RefSeq Nucleotide NM_001058 (Hs), NM_009313 (Mm), NM_012667 (Rn)
RefSeq Protein NP_001049 (Hs), NP_033339 (Mm), NP_036799 (Rn)
UniProtKB P25103 (Hs), P30548 (Mm), P14600 (Rn)
Wikipedia TACR1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of human NK1 receptor bound to the inhibitor L760735
PDB Id:  6E59
Ligand:  L760735
Resolution:  3.4Å
Species:  Human
References:  144
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the Neurokinin 1 receptor in complex with the small molecule antagonist Netupitant
PDB Id:  6HLP
Ligand:  netupitant
Resolution:  2.2Å
Species:  Human
References:  118
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the Neurokinin 1 receptor in complex with the small molecule antagonist Aprepitant
PDB Id:  6HLO
Ligand:  aprepitant
Resolution:  2.4Å
Species:  Human
References:  118
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the Neurokinin 1 receptor in complex with the small molecule antagonist CP 99994
PDB Id:  6HLL
Ligand:  CP 99994
Resolution:  3.27Å
Species:  Human
References:  118
Natural/Endogenous Ligands Click here for help
hemokinin 1 {Sp: Mouse}
neurokinin A {Sp: Human, Mouse, Rat}
neurokinin B {Sp: Human, Mouse, Rat, Pig}
neuropeptide-γ
neuropeptide K {Sp: Human, Rat}
substance P {Sp: Human, Mouse, Rat}
Comments: Substance P is the highest potency endogenous agonist
Potency order of endogenous ligands (Human)
substance P (TAC1, P20366) > neurokinin A (TAC1, P20366) > neurokinin B (TAC3, Q9UHF0)

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]BH-[Sar9,Met(O2)11]SP Peptide Ligand is labelled Ligand is radioactive Rn Full agonist 9.0 pKd 132
⤷ pKd 9.0 (Kd 1x10-9 M) [132]
[3H]BH-[Sar9,Met(O2)11]SP Peptide Ligand is labelled Ligand is radioactive Rn Full agonist 8.7 pKd 133
⤷ pKd 8.7 (Kd 2x10-9 M) [133]
[3H]SP (human, mouse, rat) Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 8.6 pKd 8
⤷ pKd 8.6 (Kd 2.8x10-9 M) [8]
hemokinin 1 {Sp: Mouse} Peptide Click here for species-specific activity table Hs Full agonist 9.8 – 11.7 pKi 12
⤷ pKi 9.8 – 11.7 [12]
substance P {Sp: Human, Mouse, Rat} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.5 – 10.3 pKi 12-13
⤷ pKi 8.5 – 10.3 [12-13]
septide Peptide Hs Full agonist 7.0 – 9.3 pKi 12,57
⤷ pKi 7.0 – 9.3 [12,57]
neurokinin A {Sp: Human, Mouse, Rat} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 6.2 – 9.3 pKi 12,44,57,116
⤷ pKi 6.2 – 9.3 [12,44,57,116]
neurokinin B {Sp: Human, Mouse, Rat, Pig} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 6.1 – 6.4 pKi 116
⤷ pKi 6.1 – 6.4 [116]
[Sar9,Met(O2)11]SP Peptide Hs Full agonist 9.7 – 9.9 pIC50 128
⤷ pIC50 9.7 – 9.9 [128]
physalaemin Peptide Hs Full agonist 9.1 – 9.2 pIC50 128
⤷ pIC50 9.1 – 9.2 [128]
eledoisin Peptide Click here for species-specific activity table Hs Full agonist 8.6 pIC50 128
⤷ pIC50 8.6 [128]
[Pro9]SP Peptide Rn Full agonist 8.6 pIC50 131
⤷ pIC50 8.6 (IC50 2.8x10-9 M) [131]
phyllomedusin Peptide Hs Full agonist 8.3 – 8.5 pIC50 128
⤷ pIC50 8.3 – 8.5 [128]
substance P-(4-11) Peptide Hs Full agonist 7.7 – 8.0 pIC50 128
⤷ pIC50 7.7 – 8.0 [128]
neuropeptide-γ Peptide Ligand is endogenous in the given species Hs Full agonist 7.6 – 7.7 pIC50 128
⤷ pIC50 7.6 – 7.7 (IC50 2.82x10-8 – 2.22x10-8 M) [128]
substance P-OMe Peptide Hs Full agonist 7.4 – 7.5 pIC50 128
⤷ pIC50 7.4 – 7.5 [128]
kassinin Peptide Click here for species-specific activity table Hs Full agonist 6.6 – 7.1 pIC50 128
⤷ pIC50 6.6 – 7.1 [128]
neuropeptide K {Sp: Human, Rat} Peptide Ligand is endogenous in the given species Hs Full agonist 6.4 – 6.5 pIC50 128
⤷ pIC50 6.4 – 6.5 [128]
substance P-(6-11) Peptide Hs Full agonist 6.3 – 6.5 pIC50 128
⤷ pIC50 6.3 – 6.5 [128]
[125I]SP (human, mouse, rat) Peptide Ligand is labelled Ligand is radioactive Hs Full agonist - -
⤷
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
spantide II Peptide Cp Antagonist 7.0 – 8.1 pA2 38,64
⤷ pA2 7.0 – 8.1 [38,64]
spantide I Peptide Cp Antagonist 7.0 – 7.1 pA2 38,64
⤷ pA2 7.0 – 7.1 [38,64]
[125I]L703,606 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 9.5 pKd 40
⤷ pKd 9.5 (Kd 3x10-10 M) [40]
vofopitant Small molecule or natural product Hs Antagonist 10.6 pKi 41
⤷ pKi 10.6 [41]
T2328 Small molecule or natural product Hs Antagonist 10.1 pKi 141
⤷ pKi 10.1 (Ki 8x10-11 M) [141]
aprepitant Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Antagonist 10.1 pKi 54-55
⤷ pKi 10.1 (Ki 9x10-11 M) [54-55]
lanepitant Small molecule or natural product Hs Antagonist 9.8 – 10.0 pKi 46
⤷ pKi 9.8 – 10.0 (Ki 1.5x10-10 – 1x10-10 M) [46]
ezlopitant Small molecule or natural product Hs Antagonist 9.7 pKi 136
⤷ pKi 9.7 (Ki 2x10-10 M) [136]
CP 99994 Small molecule or natural product Ligand has a PDB structure Hs Antagonist 9.3 – 9.7 pKi 6,116
⤷ pKi 9.3 – 9.7 [6,116]
casopitant Small molecule or natural product Hs Antagonist 9.4 pKi 62,135
⤷ pKi 9.4 [62,135]
vestipitant Small molecule or natural product Hs Antagonist 9.4 pKi 16,33
⤷ pKi 9.4 [16,33]
R116031 Small molecule or natural product Hs Antagonist 9.4 pKi 82
⤷ pKi 9.4 (Ki 4.5x10-10 M) [82]
imnopitant Small molecule or natural product Hs Antagonist 9.2 pKi 61
⤷ pKi 9.2 (Ki 5.8x10-10 M) [61]
rolapitant Small molecule or natural product Approved drug Hs Antagonist 9.2 pKi 34
⤷ pKi 9.2 (Ki 6.6x10-10 M) [34]
FK-888 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.1 pKi 65
⤷ pKi 9.1 (Ki 8x10-10 M) [65]
L-733,060 Small molecule or natural product Hs Antagonist 9.1 pKi 119
⤷ pKi 9.1 (Ki 8x10-10 M) [119]
Description: Determined as antagonism of substande P-induced calcium mobilisation in CHO cells expressing hTACR1
netupitant Small molecule or natural product Approved drug Ligand has a PDB structure Hs Antagonist 9.0 pKi 61
⤷ pKi 9.0 (Ki 9.5x10-10 M) [61]
befetupitant Small molecule or natural product Hs Antagonist 9.0 pKi 61
⤷ pKi 9.0 (Ki 1x10-9 M) [61]
SCH 206272 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.3 – 8.9 pKi 6
⤷ pKi 8.3 – 8.9 [6]
tradipitant Small molecule or natural product Immunopharmacology Ligand Hs Antagonist >7.0 pKi 4
⤷ pKi >7.0 (Ki <1x10-7 M) [4]
Description: Measuring displacement of [125I]-substance P binding to membranes from IM-9 cells (human B lymphocytes)
R-486 Peptide Hs Antagonist 6.5 – 6.6 pKi 6
⤷ pKi 6.5 – 6.6 [6]
saredutant Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.1 – 6.6 pKi 6,116
⤷ pKi 6.1 – 6.6 [6,116]
osanetant Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.0 – 6.6 pKi 6
⤷ pKi 6.0 – 6.6 [6]
spantide I Peptide Rn Antagonist 5.6 pEC50 64
⤷ pEC50 5.6 Inhibition of histamine release from peritoneal mast cells [64]
spantide II Peptide Rn Antagonist 5.5 pEC50 64
⤷ pEC50 5.5 Inhibition of histamine release from peritoneal mast cells. [64]
serlopitant Small molecule or natural product Immunopharmacology Ligand Hs Antagonist 10.2 pIC50 67
⤷ pIC50 10.2 (IC50 6x10-11 M) [67]
Description: Inhibition of binding of 125I-Substance P in vitro.
ZD6021 Small molecule or natural product Hs Antagonist 9.9 pIC50 110
⤷ pIC50 9.9 [110]
lanepitant Small molecule or natural product Hs Antagonist 9.8 pIC50 62
⤷ pIC50 9.8 (IC50 1.5x10-10 M) [62]
L760735 Small molecule or natural product Ligand has a PDB structure Hs Antagonist 9.7 pIC50 56
⤷ pIC50 9.7 (IC50 1.9x10-10 M) [56]
TAK-637 Small molecule or natural product Hs Antagonist 9.4 pIC50 89
⤷ pIC50 9.4 (IC50 4.5x10-10 M) [89]
Description: Inhibition of [125I]BH-SP binding in human IM-9 cells.
nolpitantium Small molecule or natural product Hs Antagonist 8.9 – 9.0 pIC50 128
⤷ pIC50 8.9 – 9.0 [128]
fosaprepitant Small molecule or natural product Approved drug Hs Antagonist 8.9 pIC50 54
⤷ pIC50 8.9 (IC50 1.2x10-9 M) [54]
L-732,138 Small molecule or natural product Primary target of this compound Hs Antagonist 8.6 pIC50 19
⤷ pIC50 8.6 (IC50 2.3x10-9 M) [19]
Description: Antagonism of [125]-substance P binding, to NK1 receptors expressed in CHO cells.
L-703,606 Small molecule or natural product Hs Antagonist 8.2 – 8.4 pIC50 128
⤷ pIC50 8.2 – 8.4 [128]
spantide I Peptide Oc Antagonist 8.3 pIC50 38
⤷ pIC50 8.3 (IC50 5.2x10-9 M) Measuring inhibition of contraction of the rabbit iris sphincter. [38]
spantide II Peptide Oc Antagonist 8.2 pIC50 38
⤷ pIC50 8.2 (IC50 6x10-9 M) Measuring inhibition of contraction of the rabbit iris sphincter. [38]
FK 224 Peptide Click here for species-specific activity table Hs Antagonist 7.5 – 8.3 pIC50 84
⤷ pIC50 7.5 – 8.3 [84]
RP67580 Small molecule or natural product Hs Antagonist 7.7 pIC50 39
⤷ pIC50 7.7 [39]
L-732,138 Small molecule or natural product Rn Antagonist ~6.3 pIC50 19
⤷ pIC50 ~6.3 (IC50 ~4.6x10-7 M) [19]
spantide I Peptide Rn Antagonist 5.7 pIC50 143
⤷ pIC50 5.7 (IC50 2x10-6 M) [143]
osanetant Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.6 pIC50 11
⤷ pIC50 5.6 [11]
[18F]SPA-RQ Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist - - 24
⤷ [24]
View species-specific antagonist tables
Antagonist Comments
[127] and [68] both provide evidence indicating that spantide I is an antagonist of the human NK1 receptor.
Immunopharmacology Comments
Expression in monocytes, macrophages and T helper cells suggests a role in inflammation/immunity.
Cell Type Associations
Immuno Cell Type:  T cells
Comment:  T helper cells
References:  29
Immuno Cell Type:  Macrophages & monocytes
Cell Ontology Term:   macrophage (CL:0000235)
monocyte (CL:0000576)
References:  60
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Cellular signalling
Immuno Process:  Chemotaxis & migration
Immuno Process:  Immune regulation
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family
Gq/G11 family 		Adenylyl cyclase stimulation
Phospholipase C stimulation
References:  52,74,78,88,124
Tissue Distribution Click here for help
Bone marrow stroma.
Species:  Human
Technique:  Radioligand binding.
References:  101
Brain cells.
Species:  Human
Technique:  RT-PCR.
References:  79
Colonic epithelial cells.
Species:  Human
Technique:  Western blot.
References:  45
T-Helper cells.
Species:  Human
Technique:  Antagonist effect.
References:  29
Breast cancer cells.
Species:  Human
Technique:  Western blot.
References:  21,96,104
Bone marrow fibroblasts.
Species:  Human
Technique:  Immunocytochemistry.
References:  22
Hematopoietic Progenitors (CD34+).
Species:  Human
Technique:  RT-PCR.
References:  59
Neuroblastoma.
Species:  Human
Technique:  Western blot.
References:  85
Adipose tissue, prostate, pituitary.
Species:  Human
Technique:  in situ hybridisation.
References:  17
Striatum > cerebral cortex, hippocampus, amygdala > thalamus, cerebellum.
Species:  Human
Technique:  in situ hybridisation.
References:  17
Striatum > cerebral cortex.
Species:  Human
Technique:  Autoradiography.
References:  17
Brain; pial surface, mid to upper cortical layers.
Species:  Human
Technique:  Immunohistochemistry.
References:  130
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:  129
Human arterial (umbilical) endothelium.
Species:  Human
Technique:  Autoradiography.
References:  51
Human monocytes and macrophages.
Species:  Human
Technique:  RT-PCR.
References:  60
Intestinal epithelial cells.
Species:  Human
Technique:  Autoradiography.
References:  49
Uterus.
Species:  Mouse
Technique:  Autoradiography.
References:  9
Mouse ileum; interstitial cells of Cajal at the deep muscular plexus, myoid cells of the villi.
Species:  Mouse
Technique:  Immunohistochemistry.
References:  139
Kidney.
Species:  Rat
Technique:  Autoradiography.
References:  23
Gastrointestinal tract.
Species:  Rat
Technique:  Immunohistochemistry.
References:  50
Brainstem auditory nuclei; cochlear nucleus, lateral superior olive, the medial nucleus of the trapezoid body, and inferior colliculus.
Species:  Rat
Technique:  Immunohistochemistry.
References:  53
Superior cervical ganglia.
Species:  Rat
Technique:  Quantitative autoradiography of spontaneously hypertensive rats.
References:  117
Pancreatic acini.
Species:  Rat
Technique:  immunocytochemistry.
References:  15
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 Click here for help

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

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Functional Assays Click here for help
Measurement of cAMP accumulation in COS-7 cells transfected with the human NK1.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Stimulation of cAMP accumulation.
References:  78
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:  78
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:  47
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:  10
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:  80
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:  142
Induction of tracheal smooth muscle contraction
Species:  Pig
Tissue:  Smooth muscle.
Response measured:  Tracheal contraction.
References:  121
Physiological Functions Click here for help
Release of nitric oxide.
Species:  Human
Tissue:  Endothelium of arterial vessels.
References:  95,109
Measurement of saliva production; saliva accumulated.
Species:  Rat
Tissue:  Submandibular glands.
References:  66
Measurement of saliva production; saliva not accumulated.
Species:  Mouse
Tissue:  Submandibular glands
References:  66
Induction of pressor and tachycardic effects.
Species:  Rat
Tissue: 
References:  138
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:  99
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:  98
Ganglionic NK1 receptors mediate renal nerve, heart rate and pressor response to Substance P.
Species:  Rat
Tissue:  In vivo (sympathetic ganglia).
References:  117
Initiates micturation reflex.
Species:  Rat
Tissue:  In vivo
References:  75-76,93
Stimulates licking, biting and scratching response.
Species:  Mouse
Tissue:  In vivo
References:  113-115
Mediates plasma extravasation in footpad.
Species:  Rat
Tissue:  In vivo.
References:  5
5-Hydroxytryptamine-induced tracheal contraction includes a cholinergic mechanism that requires the presence of the tachykinin NK(1) receptor.
Species:  Mouse
Tissue:  Trachea
References:  32
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:  111
Regulation of severity of acute pancreatitis and pancreatitis-associated lung injury.
Species:  Mouse
Tissue:  In vivo
References:  75
Mediation of substance P-induced edema formation.
Species:  Mouse
Tissue:  In vivo
References:  18
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:  73
Modulation of nociceptive behaviour induced by intrathecal injection of histamine.
Species:  Mouse
Tissue:  In vivo
References:  145
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:  42
NK1 receptor is required in antigen-induced cystitis.
Species:  Mouse
Tissue:  In vivo
References:  112
Activation of the NK1 receptor modulates vascular tone and permeability in the inflamed joints in knockout mice studies.
Species:  Mouse
Tissue:  In vivo
References:  70
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:  83
Grooming is induced by the NK1 agonist administered into the substantia nigra.
Species:  Rat
Tissue:  In vivo.
References:  123
Modulation of spontaneous and drug-induced locomotor activity.
Species:  Rat
Tissue:  In vivo.
References:  122
Control of presynaptic dopamine release.
Species:  Rat
Tissue:  In vivo.
References:  48,134
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:  27
Aprepitant does not reduce the incidence of post-ERCP (endoscopic retrograde cholangiopancreatography) pancreatitis in humans.
Species:  Human
Tissue:  In vivo.
References:  120
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:  26
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:  137
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:  140
Wound and tissue adhesion
Species:  Rat
Tissue:  In vivo
References:  25,69,107-108
Physiological Consequences of Altering Gene Expression Click here for help
NK1 knockout mice display an abnormal granulomatuous response in Shistosomiasis Mansoni.
Species:  Mouse
Tissue: 
Technique:  Gene knockout.
References:  14
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:  91
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
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:  71
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:  27
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:  111
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:  83
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:  86
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:  31
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:  14
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 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:  7
Disruption of noradrenaline regulation is observed in NK1 knockout mice.
Species:  Human
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  37
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:  20
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:  70
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
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 Click here for help
Disease:  Breast cancer
Disease Ontology: DOID:1612
OMIM: 114480
References:  63,81,87,90,94,96,100,105-106
Disease:  Colitis
Role:  Colonic inflammation, colonic fibrosis, colitis induced transformation
References:  30,36,45,72,77,92
Disease:  Myelofibrosis
Synonyms: Myelofibrosis with myeloid metaplasia [Orphanet: ORPHA824]
Disease Ontology: DOID:4971
OMIM: 254450
Orphanet: ORPHA824
References:  22,102-103
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 [35]. NK1 expression in pancreatic acinar cells in mice is increased during secratogogue-induced experimental pancreatitis [14]. Respiratory syncytial virus upregulates expression of NK1 in rat lungs [97]. 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 [91]. Chronic stimulation of NK1 induces ubiquitination of the receptor, which mediates its degradation and down-regulation [28].

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