INT57580

Context Info Confidence 0.69 First Reported 1994 Last Reported 2010 Negated 0 Speculated 0 Reported most in Abstract Documents 18 Total Number 18 Disease Relevance 9.35 Pain Relevance 12.47

plasma membrane (TACR1) cytoplasm (TACR1) signal transducer activity (TACR1)

Anatomy Link Frequency smooth muscle 2 neurons 2 peripheral nerve 2 spinal cord 1 central nervous system 1 TACR1 (Homo sapiens)

Pain Link Frequency Relevance Heat substance P 109 100.00 agonist 12 100.00 Kinase C 11 100.00 Morphine 24 99.98 Pain 22 99.96 spinal dorsal horn 3 99.64 Inflammation 41 99.58 dorsal root ganglion 14 98.72 Spinal cord 7 98.48 opioid receptor 13 97.72

Disease Link Frequency Relevance Heat Pain 13 99.96 Increased Venous Pressure Under Development 7 99.90 INFLAMMATION 30 99.58 Nociception 1 98.74 Ganglion Cysts 14 98.24 Hypersensitivity 4 98.12 Pulmonary Disease 6 96.66 Disease 7 96.54 Nervous System Injury 4 96.40 Neurogenic Inflammation 13 96.08

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Substance P binds to and activates the neurokinin-1 receptor with high affinity, thereby modulating several neuronal pathways including pain transmission and neurogenic inflammation.

Positive_regulation (activates) of neurokinin-1 receptor in neuronal associated with pain, inflammation, neurogenic inflammation and substance p

1) Confidence 0.69 Published 1994 Journal J. Biol. Chem. Section Abstract Doc Link 8195129 Disease Relevance 0.19 Pain Relevance 0.31

We have demonstrated a cross-desensitization between hHK-1 and [Sar9, Met (O2)11] SP substantiating NK1-receptor activation and desensitization by hHK-1.

Positive_regulation (activation) of NK1-receptor associated with substance p

2) Confidence 0.66 Published 2010 Journal Respir Res Section Body Doc Link PMC2959027 Disease Relevance 0.17 Pain Relevance 0.36

In patients with mild to moderate and strong intensity of pain, NK-1R mRNA levels were increased 14- and 30-fold over controls, respectively.

Positive_regulation (increased) of NK-1R mRNA associated with pain

3) Confidence 0.48 Published 2001 Journal Pain Section Abstract Doc Link 11275376 Disease Relevance 1.86 Pain Relevance 1.76

Tachykinins have been proposed to play an important role in human respiratory diseases such as bronchial asthma und chronic obstructive diseases (COPD) as they have been shown to have potent effects on the tone of airway smooth muscle, airway secretions, bronchial circulation and on inflammatory and immune cells by activation of the neurokinin-1 (NK-1) and neurokinin-2 (NK-2) receptors.

Positive_regulation (activation) of NK-1 in smooth muscle associated with asthma, pulmonary disease, inflammation, disease and respiratory disease

4) Confidence 0.45 Published 2006 Journal Pneumologie Section Abstract Doc Link 16463247 Disease Relevance 1.38 Pain Relevance 0.50

Tachykinins have been proposed to play an important role in human respiratory diseases such as bronchial asthma und chronic obstructive diseases (COPD) as they have been shown to have potent effects on the tone of airway smooth muscle, airway secretions, bronchial circulation and on inflammatory and immune cells by activation of the neurokinin-1 (NK-1) and neurokinin-2 (NK-2) receptors.

Positive_regulation (activation) of neurokinin-1 in smooth muscle associated with asthma, pulmonary disease, inflammation, disease and respiratory disease

5) Confidence 0.45 Published 2006 Journal Pneumologie Section Abstract Doc Link 16463247 Disease Relevance 1.38 Pain Relevance 0.50

Activation of NK-1R could then impact NF-kappaB expression and therefore may be an important participant in the effect of morphine on immune responses in the central nervous system.

Positive_regulation (Activation) of NK-1R in central nervous system associated with central nervous system and morphine

6) Confidence 0.39 Published 2004 Journal J. Neurosci. Res. Section Abstract Doc Link 14743438 Disease Relevance 0 Pain Relevance 1.45

In vitro functional assays are consistent with potent competitive antagonism of substance P-(SP) or neurokinin A-(NKA) induced [3H]-inositol phosphate accumulation in NK-1 or NK-2 monoreceptor cell lines with pA2 values of 8.19 and 8.67, respectively.

Positive_regulation (induced) of NK-1 associated with substance p

7) Confidence 0.32 Published 1996 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 8627566 Disease Relevance 0.19 Pain Relevance 0.35

Intrathecal administration of anti-recombinant human galectin-1 antibody (anti-rhGAL-1 Ab) partially but significantly attenuated the upregulation of substance P receptor (SPR) in the spinal dorsal horn and the mechanical hypersensitivity induced by the peripheral nerve injury.

Positive_regulation (upregulation) of substance P receptor in peripheral nerve associated with nervous system injury, spinal dorsal horn, hypersensitivity, peripheral nerve injury, substance p and intrathecal

8) Confidence 0.30 Published 2003 Journal Brain Res. Section Abstract Doc Link 14642832 Disease Relevance 0.89 Pain Relevance 0.83

Intrathecal administration of anti-recombinant human galectin-1 antibody (anti-rhGAL-1 Ab) partially but significantly attenuated the upregulation of substance P receptor (SPR) in the spinal dorsal horn and the mechanical hypersensitivity induced by the peripheral nerve injury.

Positive_regulation (upregulation) of SPR in peripheral nerve associated with nervous system injury, spinal dorsal horn, hypersensitivity, peripheral nerve injury, substance p and intrathecal

9) Confidence 0.30 Published 2003 Journal Brain Res. Section Abstract Doc Link 14642832 Disease Relevance 0.89 Pain Relevance 0.83

Our results indicated that, although cultured HDMEC expressed mRNA for neurokinin receptors 1, 2, and 3 (NK-1R, NK-2R, and NK-3R), SP initiated a rapid increase in HDMEC intracellular Ca2+ levels, primarily by the activation of NK-1R.

Positive_regulation (activation) of NK-1R associated with substance p

10) Confidence 0.19 Published 1998 Journal Am. J. Physiol. Section Abstract Doc Link 9843720 Disease Relevance 0.17 Pain Relevance 0.46

By using activators and inhibitors of protein kinase C (PKC) and NK1-R mutations of potential PKC phosphorylation sites, we determined the role of PKC in desensitization of responses to SP.

Positive_regulation (activators) of NK1-R associated with kinase c and substance p

11) Confidence 0.17 Published 2001 Journal Am. J. Physiol., Cell Physiol. Section Abstract Doc Link 11287322 Disease Relevance 0.20 Pain Relevance 0.68

The release of tachykinins and endothelin-3 (ET-3) from trigeminal neurons induces dural vascular permeability and vasodilatation via activation of tachykinin receptor 1 (Tacr1) and endothelin receptor type B (Ednrb) on endothelial cells.

Positive_regulation (activation) of Tacr1 in endothelial cells associated with increased venous pressure under development

12) Confidence 0.16 Published 2005 Journal Mol. Interv. Section Abstract Doc Link 16249526 Disease Relevance 0.84 Pain Relevance 0.34

These results indicated that SP might contribute to the transmission of nociceptive information and induce noxious sensation, at least in part by activating SPR in peripheral terminals of the dorsal root ganglion cells.

Positive_regulation (activating) of SPR in dorsal root ganglion associated with ganglion cysts, nociception and dorsal root ganglion

13) Confidence 0.08 Published 1998 Journal Sheng Li Xue Bao Section Abstract Doc Link 11324567 Disease Relevance 0.26 Pain Relevance 0.35

The upregulated NK-1R by morphine had functional activity, because morphine-treated cortical neurons had greater SP-induced Ca(2+) mobilization than untreated neurons.

Positive_regulation (upregulated) of NK-1R in neurons associated with substance p and morphine

14) Confidence 0.08 Published 2006 Journal J. Neurosci. Res. Section Abstract Doc Link 16983662 Disease Relevance 0.34 Pain Relevance 1.24

We assessed activation of NK1Rs by studying their internalization in spinal cord slices.

Positive_regulation (activation) of NK1Rs in spinal cord associated with spinal cord

15) Confidence 0.06 Published 1997 Journal J. Neurosci. Section Abstract Doc Link 9334388 Disease Relevance 0.09 Pain Relevance 0.69

Investigation of the mechanism(s) responsible for the morphine action showed that morphine activated NK-1R promoter and induced the phosphorylation of p38 MAPK protein in the cortical neurons.

Positive_regulation (activated) of NK-1R promoter in neurons associated with morphine

16) Confidence 0.05 Published 2006 Journal J. Neurosci. Res. Section Abstract Doc Link 16983662 Disease Relevance 0.27 Pain Relevance 1.24

Inflammation in the guinea pig induced by a resiniferatoxin challenge (with NK-1 receptor activation mediating the subsequent increase in vascular permeability) is inhibited in a dose-dependent manner by the oral preadmininstration of 17 (IC50 (1 h) = 0.008 mg/kg; IC90 (24 h) = 1.8 mg/kg), indicating that this compound has good oral bioavailbility and peripheral duration of action.

Positive_regulation (activation) of NK-1 receptor associated with inflammation

17) Confidence 0.05 Published 1998 Journal J. Med. Chem. Section Abstract Doc Link 9804700 Disease Relevance 0.15 Pain Relevance 0.24

NK-1 agonists bind to human NK-1 receptor and activate the production of both inositol phosphates and cyclic AMP.

Positive_regulation (activate) of NK-1 associated with agonist

18) Confidence 0.04 Published 1996 Journal Bioorg. Med. Chem. Section Abstract Doc Link 9022979 Disease Relevance 0.06 Pain Relevance 0.35

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