INT6727

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Context Info
Confidence 0.64
First Reported 1992
Last Reported 2010
Negated 1
Speculated 0
Reported most in Abstract
Documents 27
Total Number 36
Disease Relevance 18.75
Pain Relevance 8.71

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

aging (Ednra) plasma membrane (Ednra) signal transducer activity (Ednra)
Anatomy Link Frequency
posterior pituitary 6
vasculature 6
coronary artery 2
face 2
spinal cord 1
Ednra (Rattus norvegicus)
Pain Link Frequency Relevance Heat
agonist 56 100.00 Very High Very High Very High
antagonist 153 99.84 Very High Very High Very High
ischemia 11 99.82 Very High Very High Very High
diabetic neuropathy 1 99.76 Very High Very High Very High
Spinal cord 6 99.74 Very High Very High Very High
Eae 4 99.36 Very High Very High Very High
Nucleus accumbens 64 99.28 Very High Very High Very High
Bioavailability 51 99.26 Very High Very High Very High
tetrodotoxin 11 99.08 Very High Very High Very High
noradrenaline 2 98.68 Very High Very High Very High
Disease Link Frequency Relevance Heat
Increased Venous Pressure Under Development 298 99.92 Very High Very High Very High
Cv Unclassified Under Development 2 99.82 Very High Very High Very High
Metastasis 4 99.80 Very High Very High Very High
Diabetic Neuropathy 1 99.76 Very High Very High Very High
Disease 36 99.48 Very High Very High Very High
Natriuresis 4 99.40 Very High Very High Very High
Diabetes Mellitus 293 99.38 Very High Very High Very High
Diabetes Complications 30 99.24 Very High Very High Very High
Prostate Cancer 11 99.16 Very High Very High Very High
Injury 5 98.88 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The activation of endothelin ET(A) receptors has been implicated in diabetes-induced reductions in peripheral neurovascularization and concomitant endoneurial hypoxia.
Positive_regulation (activation) of endothelin ET associated with hypoxia and diabetes mellitus
1) Confidence 0.64 Published 2000 Journal Eur. J. Pharmacol. Section Abstract Doc Link 10657544 Disease Relevance 0.90 Pain Relevance 0.65
Activation of ET(A) receptors at the hypothalamic level inhibited, whereas ET(A) receptor activation at the posterior pituitary stimulated, neurohypophysial AVP secretion.
Positive_regulation (activation) of ET in posterior pituitary
2) Confidence 0.54 Published 2004 Journal Am. J. Physiol. Endocrinol. Metab. Section Abstract Doc Link 14665445 Disease Relevance 0 Pain Relevance 0.14
Furthermore, ET-1 and the ETA receptor are locally upregulated at the site of chronic constriction injury at both the message and the protein levels, suggesting that ET-1 may be involved in establishing pain after the injury.
Positive_regulation (upregulated) of ETA receptor associated with pain, eae and injury
3) Confidence 0.50 Published 2005 Journal Anesth. Analg. Section Abstract Doc Link 16301255 Disease Relevance 0.97 Pain Relevance 0.80
RESULTS: Both awake and anesthetized animals responded with an increase in CBV to EtOH challenge.
Positive_regulation (increase) of EtOH
4) Confidence 0.41 Published 2007 Journal J Magn Reson Imaging Section Body Doc Link 17729349 Disease Relevance 0 Pain Relevance 0
These results indicate that the systemic depressor responses induced by endothelin-1 and IRL1620 are mediated through the endothelin ETB-receptor, and the pressor responses are mediated through the endothelin ETA-receptor.
Positive_regulation (mediated) of endothelin ETB-receptor
5) Confidence 0.41 Published 1996 Journal Jpn. J. Pharmacol. Section Abstract Doc Link 8854203 Disease Relevance 0.17 Pain Relevance 0.12
Experiment 2 compared MR females with Maudsley Nonreactive (MNRA) females for 3 weeks in the conditions described above; TP exposure increased EtOH preference in MR, but not in MNRA, females.
Neg (not) Positive_regulation (increased) of EtOH
6) Confidence 0.39 Published 1995 Journal Alcohol Section Abstract Doc Link 8519443 Disease Relevance 0.08 Pain Relevance 0
Activation of ET(A) receptors at the hypothalamic level inhibited, whereas ET(A) receptor activation at the posterior pituitary stimulated, neurohypophysial AVP secretion.
Positive_regulation (Activation) of ET in posterior pituitary
7) Confidence 0.39 Published 2004 Journal Am. J. Physiol. Endocrinol. Metab. Section Abstract Doc Link 14665445 Disease Relevance 0 Pain Relevance 0.14
The impaired vasodilative responses and the reduced NO bioavailability may be addressed by an excess of ET-1 resulting in upregulation of ETA in the vascular wall, which is a consequence to diabetes, hypercholesterolemia, hypertension, and aging.
Positive_regulation (upregulation) of ETA associated with pressure and volume under development, aging, diabetes mellitus, hyperlipidemia and bioavailability
8) Confidence 0.39 Published 2010 Journal Vascular Health and Risk Management Section Body Doc Link PMC2941789 Disease Relevance 1.78 Pain Relevance 0.21
In diabetes, ET-1 levels are elevated and upregulation of ETA and ETB occurs in the vasculature, along with a reduction in NO bioavailability.1,4 Activated ET receptors can also be found in diabetic complications such as cardiomyopathy and testopathy.24–26 NOX is stimulated mainly by ETA, with PKC actively involved.27 The vasoconstrictive activity of ET-1 is mediated by the activity of NOX, and an activation of the L-type calcium channels by ET-1 causes an influx of calcium ions through activating NOX.28 An interaction of ET-1 with ROS is known as the ET–ROS pathway, which activates the ERK signaling pathway and AP-1 transcriptional factor.29 There is a positive feedback mechanism between them via an activation of ERK.
Positive_regulation (upregulation) of ETA in vasculature associated with kinase c, diabetes complications, diabetes mellitus, calcium channel, coronary heart disease and bioavailability
9) Confidence 0.39 Published 2010 Journal Vascular Health and Risk Management Section Body Doc Link PMC2941789 Disease Relevance 1.08 Pain Relevance 0.14
Role of endothelin receptor A and NADPH oxidase in vascular abnormalities

Vascular dilatation is critically impaired in many diseases and is encountered by an upregulated endothelin receptor A (ETA) in the vasculature in association with a decline in nitric oxide bioavailability.

Positive_regulation (upregulated) of endothelin receptor in vasculature associated with congenital anomalies, disease and bioavailability
10) Confidence 0.39 Published 2010 Journal Vascular Health and Risk Management Section Title Doc Link PMC2941789 Disease Relevance 0.97 Pain Relevance 0.12
Role of endothelin receptor A and NADPH oxidase in vascular abnormalities

Vascular dilatation is critically impaired in many diseases and is encountered by an upregulated endothelin receptor A (ETA) in the vasculature in association with a decline in nitric oxide bioavailability.

Positive_regulation (upregulated) of ETA in vasculature associated with congenital anomalies, disease and bioavailability
11) Confidence 0.39 Published 2010 Journal Vascular Health and Risk Management Section Title Doc Link PMC2941789 Disease Relevance 0.97 Pain Relevance 0.12
ETA receptor is activated in the resistance vessels in patients with hypertension.
Positive_regulation (activated) of ETA receptor in vessels associated with pressure and volume under development
12) Confidence 0.39 Published 2010 Journal Vascular Health and Risk Management Section Body Doc Link PMC2941789 Disease Relevance 0.87 Pain Relevance 0.03
In the renal vasculature of anesthetized rats, it is suggested that vasoconstriction is mediated through both endothelin ETA- and ETB-receptors and that endothelin ETB-receptors may be also involved in vasodilating responses to endothelin peptides.
Positive_regulation (mediated) of ETA in vasculature associated with increased venous pressure under development
13) Confidence 0.38 Published 1996 Journal Jpn. J. Pharmacol. Section Abstract Doc Link 8854203 Disease Relevance 0.25 Pain Relevance 0.06
Endothelin-1 (ET) produces contraction of cerebral resistance vessels in vitro and in situ, but also is neuroactive causing increases in tissue energy metabolism as measured by [14C]deoxyglucose autoradiography in the intact rat brain.
Positive_regulation (increases) of ET in brain
14) Confidence 0.37 Published 1992 Journal Neuropeptides Section Abstract Doc Link 1331845 Disease Relevance 0 Pain Relevance 0.08
CONCLUSIONS: These results indicate that the activation of ETA receptors in capsaicin sensitive C-fiber afferents in the bladder can induce detrusor overactivity, while ETA receptor activation in the spinal cord can inhibit the micturition reflex via activation of a spinal opioid mechanism.
Positive_regulation (activation) of ETA receptor in spinal
15) Confidence 0.37 Published 2004 Journal J. Urol. Section Body Doc Link 15371886 Disease Relevance 0 Pain Relevance 0
Either the whole explant (standard) or only the hypothalamus or posterior pituitary (compartmentalized) was exposed to log dose increases (0.01-10 nM) of the agonists ET-1 (ET(A) selective), ET-3 (nonselective), or IRL-1620 (ET(B) selective) with or without selective ET(A) (BQ-123, 2-200 nM) or ET(B) (IRL-1038, 6-600 nM) receptor antagonism.
Positive_regulation (increases) of ET in posterior pituitary associated with agonist
16) Confidence 0.36 Published 2004 Journal Am. J. Physiol. Endocrinol. Metab. Section Abstract Doc Link 14665445 Disease Relevance 0 Pain Relevance 0.12
Stimulation of ETA receptor results in a direct muscle contraction and non-ETA receptor activation facilitates the acetylcholine output from cholinergic nerve endings.
Positive_regulation (Stimulation) of ETA in muscle
17) Confidence 0.34 Published 1994 Journal Naunyn Schmiedebergs Arch. Pharmacol. Section Abstract Doc Link 7935856 Disease Relevance 0 Pain Relevance 0.26
ETA appears to be at the center in modulating the vascular activity, and an upregulated ETA has been found under multiple conditions: congestive heart failure, hypertension, atherosclerosis, endothelial dysfunction, coronary artery diseases, renal failure, cerebrovascular disease, pulmonary arterial hypertension, and sepsis.3 Interestingly, some substances and prescriptions in Traditional Chinese Medicine (TCM) may be effective in reversing endothelial insults by suppressing the activated ETA, such as quercetin, isorhamnetin, or chelerythrine (protein kinase C (PKC) inhibitor), a modified rehmannia decoction (Liu-wei-di-huang decoction), and total triterpene acids isolated from corni fructus.1,4,5
Positive_regulation (upregulated) of ETA in coronary artery associated with pressure and volume under development, heart rate under development, coronary artery disease, renal failure, increased venous pressure under development, sepsis, cerebrovascular disease, kinase c and pulmonary hypertension
18) Confidence 0.34 Published 2010 Journal Vascular Health and Risk Management Section Body Doc Link PMC2941789 Disease Relevance 1.88 Pain Relevance 0.11
It appears to be activated ETA and NADPH (nicotinamide adenine dinucleotide phosphate) oxidase in the vasculature.
Positive_regulation (activated) of ETA in vasculature
19) Confidence 0.34 Published 2010 Journal Vascular Health and Risk Management Section Abstract Doc Link PMC2941789 Disease Relevance 0.82 Pain Relevance 0.08
These mechanisms are reviewed, which include insufficient suppression of plasma renin activity and plasma aldosterone levels subsequent to salt loading, enhancement of sympathoexcitatory response in the face of a salt challenge, activation of the endothelin-1 receptor, and impaired natriuretic response to salt loading in capsaicin-pretreated rats.
Positive_regulation (activation) of endothelin-1 receptor in face associated with natriuresis and qutenza
20) Confidence 0.32 Published 2003 Journal Curr Med Chem Cardiovasc Hematol Agents Section Abstract Doc Link 15320697 Disease Relevance 0.35 Pain Relevance 1.18

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