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NK1 receptor

Family: Tachykinin receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Agonists
Antagonists
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
Clinically-Relevant Mutations and Pathophysiology
General Comments
References
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 37,113
Mouse 7 407 6 D1 Tacr1 tachykinin receptor 1 112
Rat 7 407 4q34 Tacr1 tachykinin receptor 1 50
Previous and Unofficial Names
Names References
SPR 113
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 250 (Hs), 11897 (Mm), 10685 (Rn)
DrugBank Target 427 (Hs)
Ensembl ENSG00000115353 (Hs), ENSMUSG00000030043 (Mm), ENSRNOG00000005853 (Rn)
Entrez Gene 6869 (Hs), 21336 (Mm), 24807 (Rn)
GeneCards TACR1 (Hs)
GenitoUrinary Development Molecular Anatomy Project Tacr1 (Mm)
HomoloGene 20288 (Hs)
Human Protein Reference Database 01208 (Hs)
InterPro P25103 (Hs), P30548 (Mm), P14600 (Rn)
KEGG Gene hsa:6869 (Hs), mmu:21336 (Mm), rno:24807 (Rn)
OMIM 162323 (Hs)
PharmGKB Gene PA36302 (Hs)
PhosphoSitePlus P25103 (Hs), P30548 (Mm), P14600 (Rn)
Protein Ontology (PRO) PRO:000001247 (Hs)
RefSeq Nucleotide NM_001058 (Hs), NM_009313 (Mm), NM_012667 (Rn)
RefSeq Protein NP_001049 (Hs), NP_033339 (Mm), NP_036799 (Rn)
TreeFam ENSG00000115353 (Hs), ENSMUSG00000030043 (Mm), ENSRNOG00000005853 (Rn)
UniGene Hs. 200262 (Hs)
UniProt P25103 (Hs), P30548 (Mm), P14600 (Rn)
Wikipedia NK1 receptor
Tachykinin receptors
Search for 3D structures on the PDB
Search by keyword: Tachykinin receptors NK1 receptor Search by accession number: P14600, P25103, P30548
Natural/Endogenous Ligand(s)
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 > neurokinin A > neurokinin B
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 117
hemokinin 1 {Sp: Mouse} Hs Full agonist 9.8 – 11.7 pKi 10
substance P {Sp: Human, Mouse, Rat} Hs Full agonist 8.5 – 10.3 pKi 10-11
septide Hs Full agonist 7.0 – 9.3 pKi 10,49
neurokinin A {Sp: Human, Mouse, Rat} Hs Full agonist 6.2 – 9.3 pKi 10,38,49,105
neurokinin B {Sp: Human, Mouse, Rat, Pig} Hs Full agonist 6.1 – 6.4 pKi 105
[Sar9,Met(O2)11]SP Hs Full agonist 9.7 – 9.9 pIC50 114
physalaemin Hs Full agonist 9.1 – 9.2 pIC50 114
eledoisin Hs Full agonist 8.6 pIC50 114
phyllomedusin Hs Full agonist 8.3 – 8.5 pIC50 114
substance P-(4-11) Hs Full agonist 7.7 – 8.0 pIC50 114
neuropeptide-α Hs Full agonist 7.5 – 7.7 pIC50 114
substance P-OMe Hs Full agonist 7.4 – 7.5 pIC50 114
kassinin Hs Full agonist 6.6 – 7.1 pIC50 114
neuropeptide K {Sp: Human, Rat} Hs Full agonist 6.4 – 6.5 pIC50 114
substance P-(6-11) Hs Full agonist 6.3 – 6.5 pIC50 114
spantide I Hs Full agonist 6.0 pIC50 33
spantide II Hs Full agonist 5.0 – 5.8 pIC50 33
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
aprepitant Hs Antagonist 10.7 pKi 48
vofopitant Hs Antagonist 10.6 pKi 35
T2328 Hs Antagonist 10.1 pKi 123
LY303870 Hs Antagonist 9.8 – 10.0 pKi 41
ezlopitant Hs Antagonist 9.7 pKi 119
CP 99994 Hs Antagonist 9.3 – 9.7 pKi 5,105
casopitant Hs Antagonist 9.4 pKi 54
vestipitant Hs Antagonist 9.37 pKi 14
R116031 Hs Antagonist 9.35 pKi 71
rolapitant Hs Antagonist 9.18 pKi 29
FK888 Hs Antagonist 9.1 pKi 56
netupitant Hs Antagonist 9.02 pKi 53
befetupitant Hs Antagonist 9.0 pKi 53
SCH 206272 Hs Antagonist 8.3 – 8.9 pKi 5
R-486 Hs Antagonist 6.5 – 6.6 pKi 5
saredutant Hs Antagonist 6.1 – 6.6 pKi 5,105
osanetant Hs Antagonist 6.0 – 6.6 pKi 5
ZD6021 Hs Antagonist 9.9 pIC50 99
LY303870 Hs Antagonist 9.82 pIC50 54
SR 140,333 Hs Antagonist 8.9 – 9.0 pIC50 114
L-703,606 Hs Antagonist 8.2 – 8.4 pIC50 114
FK 224 Hs Antagonist 7.5 – 8.3 pIC50 73
RP67580 Hs Antagonist 7.7 pIC50 34
osanetant Hs Antagonist 5.6 pIC50 9

Explore drug-target interactions for this set of compounds using iPHACE

Primary Transduction Mechanisms
Transducer Effector/Response
Gs family
Gq/G11 family 		Adenylate cyclase stimulation
Phospholipase C stimulation
References:  46,63,67,78,111
Tissue Distribution
Brain cells.
Species:  Human
Technique:  RT-PCR.
References:  68
Adipose tissue, prostate, pituitary.
Species:  Human
Technique:  in situ hybridisation.
References:  15
Breast cancer cells.
Species:  Human
Technique:  Western blot.
References:  18,85,93
Bone marrow fibroblasts.
Species:  Human
Technique:  Immunocytochemistry.
References:  19
Hematopoietic Progenitors (CD34+).
Species:  Human
Technique:  RT-PCR.
References:  51
Neuroblastoma.
Species:  Human
Technique:  Western blot.
References:  74
Bone marrow stroma.
Species:  Human
Technique:  Radioligand binding.
References:  90
Colonic epithelial cells.
Species:  Human
Technique:  Western blot.
References:  39
T-Helper cells.
Species:  Human
Technique:  Antagonist effect.
References:  25
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:  116
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:  115
Human arterial (umbilical) endothelium.
Species:  Human
Technique:  Autoradiography.
References:  45
Human monocytes and macrophages.
Species:  Human
Technique:  RT-PCR.
References:  52
Intestinal epithelial cells.
Species:  Human
Technique:  Autoradiography.
References:  43
Mouse ileum; interstitial cells of Cajal at the deep muscular plexus, myoid cells of the villi.
Species:  Mouse
Technique:  Immunohistochemistry.
References:  122
Uterus.
Species:  Mouse
Technique:  Autoradiography.
References:  7
Superior cervical ganglia.
Species:  Rat
Technique:  Quantitative autoradiography of spontaneously hypertensive rats.
References:  106
Kidney.
Species:  Rat
Technique:  Autoradiography.
References:  20
Pancreatic acini.
Species:  Rat
Technique:  immunocytochemistry.
References:  13
Brainstem auditory nuclei; cochlear nucleus, lateral superior olive, the medial nucleus of the trapezoid body, and inferior colliculus.
Species:  Rat
Technique:  Immunohistochemistry.
References:  47
Gastrointestinal tract.
Species:  Rat
Technique:  Immunohistochemistry.
References:  44
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 to show/hide data

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:  67
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:  67
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:  40
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:  69
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:  124
Induction of tracheal smooth muscle contraction
Species:  Pig
Tissue:  Smooth muscle.
Response measured:  Tracheal contraction.
References:  108
Physiological Functions
Release of nitric oxide.
Species:  Human
Tissue:  Endothelium of arterial vessels.
References:  84,98
Measurement of saliva production; saliva accumulated.
Species:  Rat
Tissue:  Submandibular glands.
References:  57
Measurement of saliva production; saliva not accumulated.
Species:  Mouse
Tissue:  Submandibular glands
References:  57
Induction of pressor and tachycardic effects.
Species:  Rat
Tissue: 
References:  121
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:  88
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:  87
Ganglionic NK1 receptors mediate renal nerve, heart rate and pressor response to Substance P.
Species:  Rat
Tissue:  In vivo (sympathetic ganglia).
References:  106
Initiates micturation reflex.
Species:  Rat
Tissue:  In vivo
References:  64-65,82
Stimulates licking, biting and scratching response.
Species:  Mouse
Tissue:  In vivo
References:  102-104
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:  28
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:  100
Regulation of severity of acute pancreatitis and pancreatitis-associated lung injury.
Species:  Mouse
Tissue:  In vivo
References:  64
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:  62
Modulation of nociceptive behaviour induced by intrathecal injection of histamine.
Species:  Mouse
Tissue:  In vivo
References:  125
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:  36
NK1 receptor is required in antigen-induced cystitis.
Species:  Mouse
Tissue:  In vivo
References:  101
Activation of the NK1 receptor modulates vascular tone and permeability in the inflamed joints in knockout mice studies.
Species:  Mouse
Tissue:  In vivo
References:  59
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:  72
Grooming is induced by the NK1 agonist administered into the substantia nigra.
Species:  Rat
Tissue:  In vivo.
References:  110
Modulation of spontaneous and drug-induced locomotor activity.
Species:  Rat
Tissue:  In vivo.
References:  109
Control of presynaptic dopamine release.
Species:  Rat
Tissue:  In vivo.
References:  42,118
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:  23
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:  75
Aprepitant does not reduce the incidence of post-ERCP (endoscopic retrograde cholangiopancreatography) pancreatitis in humans.
Species:  Human
Tissue:  In vivo.
References:  107
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:  22
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:  120
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:  80
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:  60
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:  23
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:  100
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:  72
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:  76
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:  27
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 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
Disruption of noradrenaline regulation is observed in NK1 knockout mice.
Species:  Human
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  32
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:  59
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:  Colitis induced transformation
References:  39,81
Mutations not determined
Disease:  Colitis
References:  26,31,61,66
Mutations not determined
Disease:  Myelofibrosis
References:  19,91-92
Mutations not determined
Disease:  Colitis fibrosis
References:  61
Mutations not determined
Disease:  Wound/Tissue adhesion
References:  21,58,96-97
Mutations not determined
Disease:  Breast cancer
References:  55,70,77,79,83,85,89,94-95
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 [30]. 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 [86]. 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 [80]. Chronic stimulation of NK1 induces ubiquitination of the receptor, which mediates its degradation and down-regulation [24].

REFERENCES

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1. Abelli, L., Somma, V., Maggi, C. A., Regoli, D., Astolfi, M., Parlani, M., Rovero, P., Conte, B. and Meli, A. (1989) Effects of tachykinins and selective tachykinin receptor agonists on vascular permeability in the rat lower urinary tract: evidence for the involvement of NK-1 receptors. J Auton Pharmacol, 9: 253-263. [PMID:2475507]

2. Ahluwalia, A., De Felipe, C., O'Brien, J., Hunt, S. P. and Perretti, M. (1998) Impaired IL-1beta-induced neutrophil accumulation in tachykinin NK1 receptor knockout mice. Br J Pharmacol, 124: 1013-1015. [PMID:9720767]

3. Altier, N. and Stewart, J. (1997) Tachykinin NK-1 and NK-3 selective agonists induce analgesia in the formalin test for tonic pain following intra-VTA or intra-accumbens microinfusions. Behav Brain Res, 89: 151-165. [PMID:9475623]

4. Andrews, P. V., Helme, R. D. and Thomas, K. L. (1989) NK-1 receptor mediation of neurogenic plasma extravasation in rat skin. Br J Pharmacol, 97: 1232-1238. [PMID:2477105]

5. Anthes, J. C., Chapman, R. W., Richard, C., Eckel, S., Corboz, M., Hey, J. A., Fernandez, X., Greenfeder, S., McLeod, R., Sehring, S., Rizzo, C., Crawley, Y., Shih, N. Y., Piwinski, J., Reichard, G., Ting, P., Carruthers, N., Cuss, F. M., Billah, M., Kreutner, W. and Egan, R. W. (2002) SCH 206272: a potent, orally active tachykinin NK(1), NK(2), and NK(3) receptor antagonist. Eur J Pharmacol, 450: 191-202. [PMID:12206858]

6. Arck, P. C., Handjiski, B., Kuhlmei, A., Peters, E. M., Knackstedt, M., Peter, A., Hunt, S. P., Klapp, B. F. and Paus, R. (2005) Mast cell deficient and neurokinin-1 receptor knockout mice are protected from stress-induced hair growth inhibition. J Mol Med, 83: 386-396. [PMID:15759104]

7. Barr, A. J., Watson, S. P., Bernal, A. L. and Nimmo, A. J. (1991) The presence of NK3 tachykinin receptors on rat uterus. Eur J Pharmacol, 203: 287-290. [PMID:1724757]

8. Bayguinov, O., Hagen, B. and Sanders, K. M. (2003) Substance P modulates localized calcium transients and membrane current responses in murine colonic myocytes. Br J Pharmacol, 138: 1233-1243. [PMID:12711623]

9. Beaujouan, J. C., Saffroy, M., Torrens, Y. and Glowinski, J. (1997) Potency and selectivity of the tachykinin NK3 receptor antagonist SR 142801. Eur J Pharmacol, 319: 307-316. [PMID:9042606]

10. Bellucci, F., Carini, F., Catalani, C., Cucchi, P., Lecci, A., Meini, S., Patacchini, R., Quartara, L., Ricci, R., Tramontana, M., Giuliani, S. and Maggi, C. A. (2002) Pharmacological profile of the novel mammalian tachykinin, hemokinin 1. Br J Pharmacol, 135: 266-274. [PMID:11786503]

11. Bennacef, I., Tymciu, S., Dhilly, M., Lasne, M. C., Debruyne, D., Perrio, C. and Barré, L. (2004) Synthesis and biological evaluation of novel fluoro and iodo quinoline carboxamides as potential ligands of NK-3 receptors for in vivo imaging studies. Bioorg Med Chem, 12: 4533-4541. [PMID:15265501]

12. Blum, A. M., Metwali, A., Kim-Miller, M., Li, J., Qadir, K., Elliott, D. E., Lu, B., Fabry, Z., Gerard, N. and Weinstock, J. V. (1999) The substance P receptor is necessary for a normal granulomatous response in murine schistosomiasis mansoni. J Immunol, 162: 6080-6085. [PMID:10229849]

13. Broccardo, M., Ciotti, M. T., Linari, G., Agostini, S., Petrella, C., Amadoro, G., Severini, C. and Improta, G. (2005) Immunocytochemical distribution of NK-1 and NK-3 tachykinin receptors in isolated pancreatic acini of guinea pigs and rats. Peptides, 26: 2351-2354. [PMID:15970359]

14. Brocco, M; Dekeyne, A; Mannoury la Cour, C; Touzard, M; Girardon, S; Veiga, S; de Nanteuil, G; deJong, TR; Olivier, B; Millan, MJ. (2008) Cellular and behavioural profile of the novel, selective neurokinin1 receptor antagonist, vestipitant: a comparison to other agents. Eur Neuropsychopharmacol, 18 (10): 729-50. [PMID:18657401]

15. Caberlotto, L., Hurd, Y. L., Murdock, P., Wahlin, J. P., Melotto, S., Corsi, M. and Carletti, R. (2003) Neurokinin 1 receptor and relative abundance of the short and long isoforms in the human brain. Eur J Neurosci, 17: 1736-1746. [PMID:12752772]

16. Cao, T., Gerard, N. P. and Brain, S. D. (1999) Use of NK(1) knockout mice to analyze substance P-induced edema formation. Am J Physiol, 277: R476-R481. [PMID:10444554]

17. Castagliuolo, I., Riegler, M., Pasha, A., Nikulasson, S., Lu, B., Gerard, C., Gerard, N. P. and Pothoulakis, C. (1998) Neurokinin-1 (NK-1) receptor is required in Clostridium difficile- induced enteritis. J Clin Invest, 101: 1547-1550. [PMID:9541482]

18. Castro, TA; Cohen, MC; Rameshwar, P. (2005) The expression of neurokinin-1 and preprotachykinin-1 in breast cancer cells depends on the relative degree of invasive and metastatic potential. Clin. Exp. Metastasis, 22 (8): 621-8. [PMID:16642400]

19. Chang, VT; Yook, C; Rameshwar, P. (2012) Synergism between fibronectin and transforming growth factor-β1 in the production of substance P in monocytes of patients with myelofibrosis. Leuk. Lymphoma,  [Epub ahead of print]. [PMID:22906243]

20. Chen, Y. and Hoover, D. B. (1995) Autoradiographic localization of NK1 and NK3 tachykinin receptors in rat kidney. Peptides, 16: 673-681. [PMID:7479302]

21. Cohen, PA; Gower, AC; Stucchi, AF; Leeman, SE; Becker, JM; Reed, KL. (2007) A neurokinin-1 receptor antagonist that reduces intraabdominal adhesion formation increases peritoneal matrix metalloproteinase activity. Wound Repair Regen, 15 (6): 800-8. [PMID:18028127]

22. Corrigan, F; Leonard, A; Ghabriel, M; Van Den Heuvel, C; Vink, R. (2012) A substance P antagonist improves outcome in female Sprague Dawley rats following diffuse traumatic brain injury. CNS Neurosci Ther, 18 (6): 513-5. [PMID:22672307]

23. Costa, S. K., Starr, A., Hyslop, S., Gilmore, D. and Brain, S. D. (2006) How important are NK(1) receptors for influencing microvascular inflammation and itch in the skin? Studies using Phoneutria nigriventer venom. Vascul Pharmacol, 45: 209-214. [PMID:16914387]

24. Cottrell, G. S., Padilla, B., Pikios, S., Roosterman, D., Steinhoff, M., Gehringer, D., Grady, E. F. and Bunnett, N. W. (2006) Ubiquitin-dependent down-regulation of the neurokinin-1 receptor. J Biol Chem, 281: 27773-27783. [PMID:16849335]

25. Cunin, P; Caillon, A; Corvaisier, M; Garo, E; Scotet, M; Blanchard, S; Delneste, Y; Jeannin, P. (2011) The tachykinins substance P and hemokinin-1 favor the generation of human memory Th17 cells by inducing IL-1β, IL-23, and TNF-like 1A expression by monocytes. J. Immunol., 186 (7): 4175-82. [PMID:21368235]

26. Dai, L; Perera, DS; King, DW; Southwell, BR; Burcher, E; Liu, L. (2012) Hemokinin-1 stimulates prostaglandin E₂ production in human colon through activation of cyclooxygenase-2 and inhibition of 15-hydroxyprostaglandin dehydrogenase. J. Pharmacol. Exp. Ther., 340 (1): 27-36. [PMID:21957267]

27. De Felipe, C., Herrero, J. F., O'Brien, J. A., Palmer, J. A., Doyle, C. A., Smith, A. J., Laird, J. M., Belmonte, C., Cervero, F. and Hunt, S. P. (1998) Altered nociception, analgesia and aggression in mice lacking the receptor for substance P. Nature, 392: 394-397. [PMID:9537323]

28. De Swert, K. O., Lefebvre, R. A., Pauwels, R. A. and Joos, G. F. (2006) Role of the tachykinin NK(1) receptor in mediating contraction to 5-hydroxytryptamine and antigen in the mouse trachea. Pulm Pharmacol Ther, : -. [PMID:16919985]

29. Duffy, RA; Morgan, C; Naylor, R; Higgins, GA; Varty, GB; Lachowicz, JE; Parker, EM. (2012) Rolapitant (SCH 619734): a potent, selective and orally active neurokinin NK1 receptor antagonist with centrally-mediated antiemetic effects in ferrets. Pharmacol. Biochem. Behav., 102 (1): 95-100. [PMID:22497992]

30. Duric, V. and McCarson, K. E. (2005) Hippocampal neurokinin-1 receptor and brain-derived neurotrophic factor gene expression is decreased in rat models of pain and stress. Neuroscience, 133: 999-1006. [PMID:15964488]

31. Engel, MA; Becker, C; Reeh, PW; Neurath, MF. (2011) Role of sensory neurons in colitis: increasing evidence for a neuroimmune link in the gut. Inflamm. Bowel Dis., 17 (4): 1030-3. [PMID:20722067]

32. Fisher, A. S., Stewart, R. J., Yan, T., Hunt, S. P. and Stanford, S. C. (2007) Disruption of noradrenergic transmission and the behavioural response to a novel environment in NK1R-/- mice. Eur J Neurosci, 25: 1195-1204. [PMID:17331215]

33. Folkers, K., Feng, D. M., Asano, N., Håkanson, R., Weisenfeld-Hallin, Z. and Leander, S. (1990) Spantide II, an effective tachykinin antagonist having high potency and negligible neurotoxicity. Proc Natl Acad Sci U S A, 87: 4833-4835. [PMID:1693780]

34. Fong, TM; Yu, H; Strader, CD. (1992) Molecular basis for the species selectivity of the neurokinin-1 receptor antagonists CP-96,345 and RP67580. J. Biol. Chem., 267 (36): 25668-71. [PMID:1281470]

35. Gardner, CJ; Armour, DR; Beattie, DT; Gale, JD; Hawcock, AB; Kilpatrick, GJ; Twissell, DJ; Ward, P. (1996) GR205171: a novel antagonist with high affinity for the tachykinin NK1 receptor, and potent broad-spectrum anti-emetic activity. Regul. Pept., 65 (1): 45-53. [PMID:8876035]

36. Gaudreau, G. A. and Plourde, V. (2003) Role of tachykinin NK1, NK2 and NK3 receptors in the modulation of visceral hypersensitivity in the rat. Neurosci Lett, 351: 59-62. [PMID:14583381]

37. Gerard, N. P., Garraway, L. A., Eddy, R. L., Shows, T. B., Iijima, H., Paquet, J. L. and Gerard, C. (1991) Human substance P receptor (NK-1): organization of the gene, chromosome localization, and functional expression of cDNA clones. Biochemistry, 30: 10640-10646. [PMID:1657150]

38. Gether, U., Marray, T., Schwartz, T. W. and Johansen, T. E. (1992) Stable expression of high affinity NK1 (substance P) and NK2 (neurokinin A) receptors but low affinity NK3 (neurokinin B) receptors in transfected CHO cells. FEBS Lett, 296: 241-244. [PMID:1311270]

39. Gillespie, E; Leeman, SE; Watts, LA; Coukos, JA; O'Brien, MJ; Cerda, SR; Farraye, FA; Stucchi, AF; Becker, JM. (2011) Truncated neurokinin-1 receptor is increased in colonic epithelial cells from patients with colitis-associated cancer. Proc. Natl. Acad. Sci. U.S.A., 108 (42): 17420-5. [PMID:21969570]

40. Gitter, B. D., Regoli, D., Howbert, J. J., Glasebrook, A. L. and Waters, D. C. (1994) Interleukin-6 secretion from human astrocytoma cells induced by substance P. J Neuroimmunol, 51: 101-108. [PMID:7512575]

41. Gitter, BD; Bruns, RF; Howbert, JJ; Waters, DC; Threlkeld, PG; Cox, LM; Nixon, JA; Lobb, KL; Mason, NR; Stengel, PW. (1995) Pharmacological characterization of LY303870: a novel, potent and selective nonpeptide substance P (neurokinin-1) receptor antagonist. J. Pharmacol. Exp. Ther., 275 (2): 737-44. [PMID:7473161]

42. Glowinski, J., Kemel, M. L., Desban, M., Gauchy, C., Lavielle, S., Chassaing, G., Beaujouan, J. C. and Tremblay, L. (1993) Distinct presynaptic control of dopamine release in striosomal- and matrix-enriched areas of the rat striatum by selective agonists of NK1, NK2 and NK3 tachykinin receptors. Regul Pept, 46: 124-128. [PMID:7692480]

43. Goode, T; O'Connell, J; Anton, P; Wong, H; Reeve, J; O'Sullivan, GC; Collins, JK; Shanahan, F. (2000) Neurokinin-1 receptor expression in inflammatory bowel disease: molecular quantitation and localisation. Gut, 47 (3): 387-96. [PMID:10940277]

44. Grady, E. F., Baluk, P., Böhm, S., Gamp, P. D., Wong, H., Payan, D. G., Ansel, J., Portbury, A. L., Furness, J. B., McDonald, D. M. and Bunnett, N. W. (1996) Characterization of antisera specific to NK1, NK2, and NK3 neurokinin receptors and their utilization to localize receptors in the rat gastrointestinal tract. J Neurosci, 16: 6975-6986. [PMID:8824334]

45. Greeno, E. W., Mantyh, P., Vercellotti, G. M. and Moldow, C. F. (1993) Functional neurokinin 1 receptors for substance P are expressed by human vascular endothelium. J Exp Med, 177: 1269-1276. [PMID:7683033]

46. Guard, S; Watson, SP. (1991) Tachykinin receptor types: Classification and membrane signalling mechanisms. Neurochem. Int., 18 (2): 149-65. [PMID:20504688]

47. Hafidi, A., Beurg, M., Bouleau, Y. and Dulon, D. (2002) Comparative distribution of NK1, NK2, and NK3 receptors in the rat brainstem auditory nuclei. Brain Res, 947: 299-306. [PMID:12176174]

48. Hale, JJ; Mills, SG; MacCoss, M; Finke, PE; Cascieri, MA; Sadowski, S; Ber, E; Chicchi, GG; Kurtz, M; Metzger, J; et al.. (1998) Structural optimization affording 2-(R)-(1-(R)-3, 5-bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4- (3-oxo-1,2,4-triazol-5-yl)methylmorpholine, a potent, orally active, long-acting morpholine acetal human NK-1 receptor antagonist. J. Med. Chem., 41 (23): 4607-14. [PMID:9804700]

49. Hastrup, H. and Schwartz, T. W. (1996) Septide and neurokinin A are high-affinity ligands on the NK-1 receptor: evidence from homologous versus heterologous binding analysis. FEBS Lett, 399: 264-266. [PMID:8985159]

50. Hershey, A. D., Dykema, P. E. and Krause, J. E. (1991) Organization, structure, and expression of the gene encoding the rat substance P receptor. J Biol Chem, 266: 4366-4374. [PMID:1705552]

51. Hiramoto, M; Aizawa, S; Iwase, O; Nakano, M; Toyama, K; Hoque, M; Nabeshima, R; Kaidow, A; Imai, T; Hoshi, H; et al.. (1998) Stimulatory effects of substance P on CD34 positive cell proliferation and differentiation in vitro are mediated by the modulation of stromal cell function. Int. J. Mol. Med., 1 (2): 347-54. [PMID:9852236]

52. Ho, W. Z., Lai, J. P., Zhu, X. H., Uvaydova, M. and Douglas, S. D. (1997) Human monocytes and macrophages express substance P and neurokinin-1 receptor. J Immunol, 159: 5654-5660. [PMID:9548509]

53. Hoffmann, T; Bös, M; Stadler, H; Schnider, P; Hunkeler, W; Godel, T; Galley, G; Ballard, TM; Higgins, GA; Poli, SM; et al.. (2006) Design and synthesis of a novel, achiral class of highly potent and selective, orally active neurokinin-1 receptor antagonists. Bioorg. Med. Chem. Lett., 16 (5): 1362-5. [PMID:16332435]

54. Huang, SC; Korlipara, VL. (2010) Neurokinin-1 receptor antagonists: a comprehensive patent survey. Expert Opin Ther Pat, 20 (8): 1019-45. [PMID:20533894]

55. Huang, WQ; Wang, JG; Chen, L; Wei, HJ; Chen, H. (2010) SR140333 counteracts NK-1 mediated cell proliferation in human breast cancer cell line T47D. J. Exp. Clin. Cancer Res., 29: 55. [PMID:20497542]

56. Ichinose, M; Miura, M; Yamauchi, H; Kageyama, N; Tomaki, M; Oyake, T; Ohuchi, Y; Hida, W; Miki, H; Tamura, G; et al.. (1996) A neurokinin 1-receptor antagonist improves exercise-induced airway narrowing in asthmatic patients. Am. J. Respir. Crit. Care Med., 153 (3): 936-41. [PMID:8630576]

57. Iwabuchi, Y., Aoki, C. and Masuhara, T. (1989) Effects of tachykinins on the secretion of fluid and glycoproteins from the submandibular glands of rat, mouse, hamster and guinea pig. Jpn J Pharmacol, 51: 428-431. [PMID:2482911]

58. Katayama, I; Nishioka, K. (1997) Substance P augments fibrogenic cytokine-induced fibroblast proliferation: possible involvement of neuropeptide in tissue fibrosis. J. Dermatol. Sci., 15 (3): 201-6. [PMID:9302648]

59. Keeble, J., Blades, M., Pitzalis, C., Castro da Rocha, F. A. and Brain, S. D. (2005) The role of substance P in microvascular responses in murine joint inflammation. Br J Pharmacol, 144: 1059-1066. [PMID:15700029]

60. Kidd, B. L., Inglis, J. J., Vetsika, K., Hood, V. C., De Felipe, C., Bester, H., Hunt, S. P. and Cruwys, S. C. (2003) Inhibition of inflammation and hyperalgesia in NK-1 receptor knock-out mice. Neuroreport, 14: 2189-2192. [PMID:14625445]

61. Koon, HW; Shih, D; Karagiannides, I; Zhao, D; Fazelbhoy, Z; Hing, T; Xu, H; Lu, B; Gerard, N; Pothoulakis, C. (2010) Substance P modulates colitis-associated fibrosis. Am. J. Pathol., 177 (5): 2300-9. [PMID:20889569]

62. Kramer, M. S., Cutler, N., Feighner, J., Shrivastava, R., Carman, J., Sramek, J. J., Reines, S. A., Liu, G., Snavely, D., Wyatt-Knowles, E., Hale, J. J., Mills, S. G., MacCoss, M., Swain, C. J., Harrison, T., Hill, R. G., Hefti, F., Scolnick, E. M., Cascieri, M. A., Chicchi, G. G., Sadowski, S., Williams, A. R., Hewson, L., Smith, D., Carlson, E. J., Hargreaves, R. J. and Rupniak, N. M. (1998) Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science, 281: 1640-1645. [PMID:9733503]

63. Laniyonu, A; Sliwinski-Lis, E; Fleming, N. (1988) Different tachykinin receptor subtypes are coupled to the phosphoinositide or cyclic AMP signal transduction pathways in rat submandibular cells. FEBS Lett., 240 (1-2): 186-90. [PMID:2461321]

64. Lecci, A., Giuliani, S. and Maggi, C. A. (1992) Effect of the NK-1 receptor antagonist GR 82,334 on reflexly-induced bladder contractions. Life Sci, 51: PL277-PL280. [PMID:1335533]

65. Lecci, A., Giuliani, S., Patacchini, R. and Maggi, C. A. (1993) Evidence against a peripheral role of tachykinins in the initiation of micturition reflex in rats. J Pharmacol Exp Ther, 264: 1327-1332. [PMID:8383746]

66. Liu, L; Markus, I; Saghire, HE; Perera, DS; King, DW; Burcher, E. (2011) Distinct differences in tachykinin gene expression in ulcerative colitis, Crohn's disease and diverticular disease: a role for hemokinin-1?. Neurogastroenterol. Motil., 23 (5): 475-83, e179-80. [PMID:21342363]

67. Martini, L., Hastrup, H., Holst, B., Fraile-Ramos, A., Marsh, M. and Schwartz, T. W. (2002) NK1 receptor fused to beta-arrestin displays a single-component, high-affinity molecular phenotype. Mol Pharmacol, 62: 30-37. [PMID:12065752]

68. Massillon, D; Chen, W; Hawkins, M; Liu, R; Barzilai, N; Rossetti, L. (1995) Quantitation of hepatic glucose fluxes and pathways of hepatic glycogen synthesis in conscious mice. Am. J. Physiol., 269 (6 Pt 1): E1037-43. [PMID:8572194]

69. Mau, S. E., Larsen, P. J., Mikkelsen, J. A. and Saermark, T. (1990) Substance P and related tachykinins induce receptor-mediated hydrolysis of polyphosphoinositides in the rat anterior pituitary. Mol Cell Endocrinol, 69: 69-78. [PMID:1691115]

70. Mayordomo, C; García-Recio, S; Ametller, E; Fernández-Nogueira, P; Pastor-Arroyo, EM; Vinyals, L; Casas, I; Gascón, P; Almendro, V. (2012) Targeting of substance P induces cancer cell death and decreases the steady state of EGFR and Her2. J. Cell. Physiol., 227 (4): 1358-66. [PMID:21604273]

71. Megens, AA; Ashton, D; Vermeire, JC; Vermote, PC; Hens, KA; Hillen, LC; Fransen, JF; Mahieu, M; Heylen, L; Leysen, JE; et al.. (2002) Pharmacological profile of (2R-trans)-4-[1-[3,5-bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-piperidinyl]-N-(2,6-dimethylphenyl)-1-acetamide (S)-Hydroxybutanedioate (R116301), an orally and centrally active neurokinin-1 receptor antagonist. J. Pharmacol. Exp. Ther., 302 (2): 696-709. [PMID:12130734]

72. Morcuende, S., Gadd, C. A., Peters, M., Moss, A., Harris, E. A., Sheasby, A., Fisher, A. S., De Felipe, C., Mantyh, P. W., Rupniak, N. M., Giese, K. P. and Hunt, S. P. (2003) Increased neurogenesis and brain-derived neurotrophic factor in neurokinin-1 receptor gene knockout mice. Eur J Neurosci, 18: 1828-1836. [PMID:14622216]

73. Morimoto, H., Murai, M., Maeda, Y., Yamaoka, M., Nishikawa, M., Kiyotoh, S. and Fujii, T. (1992) FK 224, a novel cyclopeptide substance P antagonist with NK1 and NK2 receptor selectivity. J Pharmacol Exp Ther, 262: 398-402. [PMID:1378096]

74. Mukerji, I; Ramkissoon, SH; Reddy, KK; Rameshwar, P. (2005) Autocrine proliferation of neuroblastoma cells is partly mediated through neurokinin receptors: relevance to bone marrow metastasis. J. Neurooncol., 71 (2): 91-8. [PMID:15690122]

75. Murakami, T; Ozasa, H; Suzuki, T. (1990) [Respiratory failure in acute fulminant pancreatitis]. Nippon Rinsho, 48 (1): 134-9. [PMID:2304265]

76. Musazzi, L., Perez, J., Hunt, S. P., Racagni, G. and Popoli, M. (2005) Changes in signaling pathways regulating neuroplasticity induced by neurokinin 1 receptor knockout. Eur J Neurosci, 21: 1370-1378. [PMID:15813946]

77. Muñoz, M; Rosso, M; Casinello, F; Coveñas, R. (2010) Paravertebral anesthesia: how substance P and the NK-1 receptor could be involved in regional block and breast cancer recurrence. Breast Cancer Res. Treat., 122 (2): 601-3. [PMID:20333544]

78. Nakajima, Y; Tsuchida, K; Negishi, M; Ito, S; Nakanishi, S. (1992) Direct linkage of three tachykinin receptors to stimulation of both phosphatidylinositol hydrolysis and cyclic AMP cascades in transfected Chinese hamster ovary cells. J. Biol. Chem., 267 (4): 2437-42. [PMID:1370820]

79. Navarro, P; Ramkissoon, SH; Shah, S; Park, JM; Murthy, RG; Patel, SA; Greco, SJ; Rameshwar, P. (2012) An indirect role for the oncomir-519b in the expression of truncated neurokinin-1 in breast cancer cells. Exp. Cell Res., 318 (20): 2604-15. [PMID:22981979]

80. Nichols, M. L., Allen, B. J., Rogers, S. D., Ghilardi, J. R., Honore, P., Luger, N. M., Finke, M. P., Li, J., Lappi, D. A., Simone, D. A. and Mantyh, P. W. (1999) Transmission of chronic nociception by spinal neurons expressing the substance P receptor. Science, 286: 1558-1561. [PMID:10567262]

81. Pagán, B; Isidro, AA; Coppola, D; Chen, Z; Ren, Y; Wu, J; Appleyard, CB. (2010) Effect of a neurokinin-1 receptor antagonist in a rat model of colitis-associated colon cancer. Anticancer Res., 30 (9): 3345-53. [PMID:20944107]

82. Palea, S., Dalforno, G., Gaviraghi, G., Hagan, R. M., Trist, D. G. and Pietra, C. (1993) Further studies on the effects of selective neurokinin agonists upon the activation of micturition reflex in rats. Evidence for a dual NK-1 receptor mediated excitatory and inhibitory activity. Neuropeptides, 24: 285-291. [PMID:7687043]

83. Palma, C. (2006) Tachykinins and their receptors in human malignancies. Curr Drug Targets, 7 (8): 1043-52. [PMID:16918332]

84. Palmer, R. M., Ferrige, A. G. and Moncada, S. (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature, 327: 524-526. [PMID:3495737]

85. Patel, HJ; Ramkissoon, SH; Patel, PS; Rameshwar, P. (2005) Transformation of breast cells by truncated neurokinin-1 receptor is secondary to activation by preprotachykinin-A peptides. Proc. Natl. Acad. Sci. U.S.A., 102 (48): 17436-41. [PMID:16291810]

86. Piedimonte, G., Rodriguez, M. M., King, K. A., McLean, S. and Jiang, X. (1999) Respiratory syncytial virus upregulates expression of the substance P receptor in rat lungs. Am J Physiol, 277: L831-L840. [PMID:10516226]

87. Placenza, F. M., Fletcher, P. J., Vaccarino, F. J. and Erb, S. (2006) Effects of central neurokinin-1 receptor antagonism on cocaine- and opiate-induced locomotor activity and self-administration behaviour in rats. Pharmacol Biochem Behav, 84: 94-101. [PMID:16757018]

88. Placenza, F. M., Vaccarino, F. J., Fletcher, P. J. and Erb, S. (2005) Activation of central neurokinin-1 receptors induces reinstatement of cocaine-seeking behavior. Neurosci Lett, 390: 42-47. [PMID:16125318]

89. Rameshwar, P. (2007) Implication of possible therapies targeted for the tachykinergic system with the biology of neurokinin receptors and emerging related proteins. Recent Pat CNS Drug Discov, 2 (1): 79-84. [PMID:18221219]

90. Rameshwar, P; Gascón, P. (1995) Substance P (SP) mediates production of stem cell factor and interleukin-1 in bone marrow stroma: potential autoregulatory role for these cytokines in SP receptor expression and induction. Blood, 86 (2): 482-90. [PMID:7541664]

91. Rameshwar, P; Joshi, DD; Yadav, P; Qian, J; Gascon, P; Chang, VT; Anjaria, D; Harrison, JS; Song, X. (2001) Mimicry between neurokinin-1 and fibronectin may explain the transport and stability of increased substance P immunoreactivity in patients with bone marrow fibrosis. Blood, 97 (10): 3025-31. [PMID:11342427]

92. Rameshwar, P; Oh, HS; Yook, C; Gascon, P; Chang, VT. (2003) Substance p-fibronectin-cytokine interactions in myeloproliferative disorders with bone marrow fibrosis. Acta Haematol., 109 (1): 1-10. [PMID:12486316]

93. Ramkissoon, SH; Patel, PS; Taborga, M; Rameshwar, P. (2007) Nuclear factor-kappaB is central to the expression of truncated neurokinin-1 receptor in breast cancer: implication for breast cancer cell quiescence within bone marrow stroma. Cancer Res., 67 (4): 1653-9. [PMID:17308106]

94. Reddy, BY; Greco, SJ; Patel, PS; Trzaska, KA; Rameshwar, P. (2009) RE-1-silencing transcription factor shows tumor-suppressor functions and negatively regulates the oncogenic TAC1 in breast cancer cells. Proc. Natl. Acad. Sci. U.S.A., 106 (11): 4408-13. [PMID:19246391]

95. Reddy, BY; Trzaska, KA; Murthy, RG; Navarro, P; Rameshwar, P. (2008) Neurokinin receptors as potential targets in breast cancer treatment. Curr Drug Discov Technol, 5 (1): 15-9. [PMID:18537563]

96. Reed, KL; Fruin, AB; Bishop-Bartolomei, KK; Gower, AC; Nicolaou, M; Stucchi, AF; Leeman, SE; Becker, JM. (2002) Neurokinin-1 receptor and substance P messenger RNA levels increase during intraabdominal adhesion formation. J. Surg. Res., 108 (1): 165-72. [PMID:12443729]

97. Reed, KL; Fruin, AB; Gower, AC; Stucchi, AF; Leeman, SE; Becker, JM. (2004) A neurokinin 1 receptor antagonist decreases postoperative peritoneal adhesion formation and increases peritoneal fibrinolytic activity. Proc. Natl. Acad. Sci. U.S.A., 101 (24): 9115-20. [PMID:15187234]

98. Regoli, D., Boudon, A. and Fauchere, J. L. (1994) Receptors and antagonists for substance P and related peptides. Pharmacol Rev, 46: 551-599. [PMID:7534932]

99. Rumsey, W. L., Aharony, D., Bialecki, R. A., Abbott, B. M., Barthlow, H. G., Caccese, R., Ghanekar, S., Lengel, D., McCarthy, M., Wenrich, B., Undem, B., Ohnmacht, C., Shenvi, A., Albert, J. S., Brown, F., Bernstein, P. R. and Russell, K. (2001) Pharmacological characterization of ZD6021: a novel, orally active antagonist of the tachykinin receptors. J Pharmacol Exp Ther, 298: 307-315. [PMID:11408556]

100. Rupniak, N. M., Carlson, E. J., Webb, J. K., Harrison, T., Porsolt, R. D., Roux, S., De Felipe, C., Hunt, S. P., Oates, B. and Wheeldon, A. (2001) Comparison of the phenotype of NK1R-/- mice with pharmacological blockade of the substance P (NK1 ) receptor in assays for antidepressant and anxiolytic drugs. Behav Pharmacol, 12: 497-508. [PMID:11742144]

101. Saban, R., Saban, M. R., Nguyen, N. B., Lu, B., Gerard, C., Gerard, N. P. and Hammond, T. G. (2000) Neurokinin-1 (NK-1) receptor is required in antigen-induced cystitis. Am J Pathol, 156: 775-780. [PMID:10702392]

102. Sakurada, T., Tan-no, K., Yamada, T., Sakurada, S., Kisara, K., Ohba, M. and Terenius, L. (1990) N-terminal substance P fragments inhibit the spinally induced, NK 1 receptor mediated behavioural responses in mice. Life Sci, 47: PL109-PL113. [PMID:1701844]

103. Sakurada, T., Yamada, T., Sakurada, S., Kisara, K. and Ohba, M. (1989) Substance P analogues containing D-histidine antagonize the behavioural effects of intrathecally co-administered substance P in mice. Eur J Pharmacol, 174: 153-160. [PMID:2483548]

104. Sakurada, T., Yamada, T., Tan-no, K., Manome, Y., Sakurada, S., Kisara, K. and Ohba, M. (1991) Differential effects of substance P analogs on neurokinin 1 receptor agonists in the mouse spinal cord. J Pharmacol Exp Ther, 259: 205-210. [PMID:1717679]

105. Sarau, H. M., Griswold, D. E., Potts, W., Foley, J. J., Schmidt, D. B., Webb, E. F., Martin, L. D., Brawner, M. E., Elshourbagy, N. A., Medhurst, A. D., Giardina, G. A. and Hay, D. W. (1997) Nonpeptide tachykinin receptor antagonists: I. Pharmacological and pharmacokinetic characterization of SB 223412, a novel, potent and selective neurokinin-3 receptor antagonist. J Pharmacol Exp Ther, 281: 1303-1311. [PMID:9190866]

106. Schoborg, R. V., Hoover, D. B., Tompkins, J. D. and Hancock, J. C. (2000) Increased ganglionic responses to substance P in hypertensive rats due to upregulation of NK(1) receptors. Am J Physiol Regul Integr Comp Physiol, 279: R1685-R1694. [PMID:11049850]

107. Shah, TU; Liddle, R; Branch, MS; Jowell, P; Obando, J; Poleski, M. (2012) Pilot study of aprepitant for prevention of post-ERCP pancreatitis in high risk patients: a phase II randomized, double-blind placebo controlled trial. JOP, 13 (5): 514-8. [PMID:22964958]

108. Sheldrick, RL; Ball, DI; Coleman, RA. (1990) Characterisation of the neurokinin receptors mediating contraction of isolated tracheal preparations from a variety of species. Agents Actions Suppl., 31: 205-9. [PMID:1706905]

109. Stoessl, A. J., Dourish, C. T. and Iversen, S. D. (1988) The NK-3 tachykinin receptor agonist senktide elicits 5-HT-mediated behaviour following central or peripheral administration in mice and rats. Br J Pharmacol, 94: 285-287. [PMID:2456111]

110. Stoessl, A. J., Szczutkowski, E., Glenn, B. and Watson, I. (1991) Behavioural effects of selective tachykinin agonists in midbrain dopamine regions. Brain Res, 565: 254-262. [PMID:1668812]

111. Stratowa, C., Machat, H., Burger, E., Himmler, A., Schafer, R., Spevak, W., Weyer, U., Wiche-Castanon, M. and Czernilofsky, A. P. (1995) Functional characterization of the human neurokinin receptors NK1, NK2, and NK3 based on a cellular assay system. J Recept Signal Transduct Res, 15: 617-630. [PMID:8903968]

112. Sundelin, J. B., Provvedini, D. M., Wahlestedt, C. R., Laurell, H., Pohl, J. S. and Peterson, P. A. (1992) Molecular cloning of the murine substance K and substance P receptor genes. Eur J Biochem, 203: 625-631. [PMID:1370937]

113. Takeda, Y., Chou, K. B., Takeda, J., Sachais, B. S. and Krause, J. E. (1991) Molecular cloning, structural characterization and functional expression of the human substance P receptor. Biochem Biophys Res Commun, 179: 1232-1240. [PMID:1718267]

114. Tian, Y., Wu, L. H., Oxender, D. L. and Chung, F. Z. (1996) The unpredicted high affinities of a large number of naturally occurring tachykinins for chimeric NK1/NK3 receptors suggest a role for an inhibitory domain in determining receptor specificity. J Biol Chem, 271: 20250-20257. [PMID:8702757]

115. Tooney, P. A., Au, G. G. and Chahl, L. A. (2000) Localisation of tachykinin NK1 and NK3 receptors in the human prefrontal and visual cortex. Neurosci Lett, 283: 185-188. [PMID:10754218]

116. Tooney, P. A., Au, G. G. and Chahl, L. A. (2000) Tachykinin NK1 and NK3 receptors in the prefrontal cortex of the human brain. Clin Exp Pharmacol Physiol, 27: 947-949. [PMID:11071316]

117. Tousignant, C; Guillemette, G; Drapeau, G; Télémaque, S; Dion, S; Regoli, D. (1990) 125I-BH[Sar9, Met(O2)11]-SP, a new selective ligand for the NK-1 receptor in the central nervous system. Brain Res., 524 (2): 263-70. [PMID:1705465]

118. Tremblay, L., Kemel, M. L., Desban, M., Gauchy, C. and Glowinski, J. (1992) Distinct presynaptic control of dopamine release in striosomal- and matrix-enriched areas of the rat striatum by selective agonists of NK1, NK2, and NK3 tachykinin receptors. Proc Natl Acad Sci U S A, 89: 11214-11218. [PMID:1280822]

119. Tsuchiya, M; Fujiwara, Y; Kanai, Y; Mizutani, M; Shimada, K; Suga, O; Ueda, S; Watson, JW; Nagahisa, A. (2002) Anti-emetic activity of the novel nonpeptide tachykinin NK1 receptor antagonist ezlopitant (CJ-11,974) against acute and delayed cisplatin-induced emesis in the ferret. Pharmacology, 66 (3): 144-52. [PMID:12372904]

120. Tumati, S; Largent-Milnes, TM; Keresztes, AI; Yamamoto, T; Vanderah, TW; Roeske, WR; Hruby, VJ; Varga, EV. (2012) Tachykinin NK₁ receptor antagonist co-administration attenuates opioid withdrawal-mediated spinal microglia and astrocyte activation. Eur. J. Pharmacol., 684 (1-3): 64-70. [PMID:22724132]

121. Unger, T., Carolus, S., Demmert, G., Ganten, D., Lang, R. E., Maser-Gluth, C., Steinberg, H. and Veelken, R. (1988) Substance P induces a cardiovascular defense reaction in the rat: pharmacological characterization. Circ Res, 63: 812-820. [PMID:2458861]

122. Vannucchi, M. G. and Faussone-Pellegrini, M. S. (2000) NK1, NK2 and NK3 tachykinin receptor localization and tachykinin distribution in the ileum of the mouse. Anat Embryol (Berl), 202: 247-255. [PMID:10994997]

123. Watanabe, Y; Asai, H; Ishii, T; Kiuchi, S; Okamoto, M; Taniguchi, H; Nagasaki, M; Saito, A. (2008) Pharmacological characterization of T-2328, 2-fluoro-4'-methoxy-3'-[[[(2S,3S)-2-phenyl-3-piperidinyl]amino]methyl]-[1,1'-biphenyl]-4-carbonitrile dihydrochloride, as a brain-penetrating antagonist of tachykinin NK1 receptor. J. Pharmacol. Sci., 106 (1): 121-7. [PMID:18187929]

124. Williams, R., Zou, X. and Hoyle, G. W. (2007) Tachykinin-1 receptor stimulates proinflammatory gene expression in lung epithelial cells through activation of NF-kappaB via a G(q)-dependent pathway. Am J Physiol Lung Cell Mol Physiol, 292: L430-L437. [PMID:17041011]

125. Yoshida, A., Mobarakeh, J. I., Sakurai, E., Sakurada, S., Orito, T., Kuramasu, A., Kato, M. and Yanai, K. (2005) Intrathecally-administered histamine facilitates nociception through tachykinin NK1 and histamine H1 receptors: a study in histidine decarboxylase gene knockout mice. Eur J Pharmacol, 522: 55-62. [PMID:16212954]

To cite this database page, please use the following:

Steven D. Douglas, Susan E. Leeman, Jeffrey Barrett, Erin Dombrowsky, Christa Y. Heyward, Pranela Remeshwar.
Tachykinin receptors: NK1 receptor. Last modified on 11/03/2013. Accessed on 18/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=360.


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