INT70905

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Context Info
Confidence 0.67
First Reported 1997
Last Reported 2010
Negated 0
Speculated 1
Reported most in Body
Documents 49
Total Number 50
Disease Relevance 24.33
Pain Relevance 11.79

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

cell proliferation (EDNRA) signal transduction (EDNRA) aging (EDNRA)
plasma membrane (EDNRA) signal transducer activity (EDNRA)
Anatomy Link Frequency
plasma 2
blood 2
skin 2
heart 2
smooth muscle 1
EDNRA (Homo sapiens)
Pain Link Frequency Relevance Heat
antagonist 335 99.96 Very High Very High Very High
melanocortin 1 receptor 37 99.88 Very High Very High Very High
Kinase C 86 99.84 Very High Very High Very High
Kappa opioid receptor 1 99.72 Very High Very High Very High
bradykinin 69 99.68 Very High Very High Very High
Inflammation 86 99.00 Very High Very High Very High
Intracerebroventricular 1 98.94 Very High Very High Very High
Dismenorea 3 98.82 Very High Very High Very High
adenocard 10 98.76 Very High Very High Very High
qutenza 240 98.72 Very High Very High Very High
Disease Link Frequency Relevance Heat
Increased Venous Pressure Under Development 272 99.84 Very High Very High Very High
Papillomavirus Infection 20 99.36 Very High Very High Very High
Hypoxia 64 99.34 Very High Very High Very High
Cancer 219 99.24 Very High Very High Very High
Pressure And Volume Under Development 83 99.16 Very High Very High Very High
Injury 37 99.12 Very High Very High Very High
INFLAMMATION 88 99.00 Very High Very High Very High
Dysmenorrhea 3 98.82 Very High Very High Very High
Pulmonary Hypertension 637 98.76 Very High Very High Very High
Diabetes Mellitus 183 98.68 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Upregulation of ETA receptors and downregulation of ETB receptors in the brainstem with high doses of morphine may indicate possible effects on cerebral vascular tone.
Positive_regulation (Upregulation) of ETA in brainstem associated with medulla and morphine
1) Confidence 0.67 Published 1998 Journal Can. J. Physiol. Pharmacol. Section Abstract Doc Link 9795754 Disease Relevance 0 Pain Relevance 0.64
The authors concluded that the ET-1 levels are increased primarily because of excess synthesis rather than reduced clearance of ET-1.


Positive_regulation (increased) of ET
2) Confidence 0.56 Published 2008 Journal European Heart Journal Section Body Doc Link PMC2515885 Disease Relevance 0.66 Pain Relevance 0.09
The observation that 5-HT1B receptor activation can potentiate Gq-coupled receptor stimulated second messenger responses may have an important physiological role in the regulation of vascular smooth muscle contraction.
Positive_regulation (activation) of Gq-coupled receptor in smooth muscle
3) Confidence 0.51 Published 1998 Journal Eur. J. Pharmacol. Section Abstract Doc Link 9652344 Disease Relevance 0.17 Pain Relevance 0.27
In contrast, bosentan and less-selective ETA-receptor antagonists (ETA:ETB ratio <2000:1) increase plasma ET-1 in healthy volunteers and in patients with heart failure or PAH (TableĀ 1).
Positive_regulation (increase) of ET in heart associated with pulmonary hypertension, heart rate under development and antagonist
4) Confidence 0.49 Published 2008 Journal European Heart Journal Section Body Doc Link PMC2515885 Disease Relevance 0.53 Pain Relevance 0.08
The recent identification of high-selective small molecules that inhibit ligand-induced activation of ETAR offers now the possibility of testing this therapeutic approach in a clinical setting.
Positive_regulation (activation) of ETAR
5) Confidence 0.45 Published 2004 Journal J Transl Med Section Body Doc Link PMC436068 Disease Relevance 1.41 Pain Relevance 0.79
For example, the ETRA ambrisentan has been reported to have an ETA:ETB selectivity ranging from 29:1 for ET-1-mediated contraction in the rat aorta32 to 4000:1 in myocardial membranes.33
Positive_regulation (29:1) of ET
6) Confidence 0.41 Published 2008 Journal European Heart Journal Section Body Doc Link PMC2515885 Disease Relevance 0.41 Pain Relevance 0.10
Interestingly, significant increases of ET-1 levels occurring 2 h following ingestion have been reported with ambrisentan (widely reported to be selective for ETA), suggesting that its functional selectivity may differ from that observed in vitro.35 Whether elevated ET-1 levels seen in ETRA-treated PAH patients have pathophysiological or prognostic significance remains unknown.


Positive_regulation (increases) of ET associated with pulmonary hypertension
7) Confidence 0.41 Published 2008 Journal European Heart Journal Section Body Doc Link PMC2515885 Disease Relevance 0.63 Pain Relevance 0.10
Interestingly, significant increases of ET-1 levels occurring 2 h following ingestion have been reported with ambrisentan (widely reported to be selective for ETA), suggesting that its functional selectivity may differ from that observed in vitro.35 Whether elevated ET-1 levels seen in ETRA-treated PAH patients have pathophysiological or prognostic significance remains unknown.


Spec (Whether) Positive_regulation (elevated) of ET associated with pulmonary hypertension
8) Confidence 0.41 Published 2008 Journal European Heart Journal Section Body Doc Link PMC2515885 Disease Relevance 0.80 Pain Relevance 0.11
METHODS: This study included 46 consecutive patients who underwent ETAR for rectal adenocarcinoma between October 1992 and October 2000.
Positive_regulation (underwent) of ETAR
9) Confidence 0.40 Published 2003 Journal Surg Endosc Section Body Doc Link 12582765 Disease Relevance 0.10 Pain Relevance 0
METHODS: Outcome in patients who underwent ETAR with a urologic resectoscope between October 1992 and March 1999 are reported.
Positive_regulation (underwent) of ETAR
10) Confidence 0.40 Published 2001 Journal Gastroenterol. Clin. Biol. Section Body Doc Link 11845045 Disease Relevance 0.10 Pain Relevance 0
Interestingly, sitaxentan,43 but not bosentan,39 prevented the increase in ET-1 levels when treatment was initiated early, with hypoxia.
Positive_regulation (increase) of ET associated with hypoxia
11) Confidence 0.38 Published 2008 Journal European Heart Journal Section Body Doc Link PMC2515885 Disease Relevance 0.75 Pain Relevance 0.07
Circulating plasma ET-1 levels are elevated in atherosclerosis, arterial hypertension, heart failure, and PAH11 when compared with the normal state.
Positive_regulation (elevated) of ET in heart associated with heart rate under development, pressure and volume under development and increased venous pressure under development
12) Confidence 0.38 Published 2008 Journal European Heart Journal Section Body Doc Link PMC2515885 Disease Relevance 0.84 Pain Relevance 0.04
In contrast, late treatment, 2 weeks after initiation of hypoxia, did not affect the established elevation of ET-1 level.


Positive_regulation (elevation) of ET associated with hypoxia
13) Confidence 0.38 Published 2008 Journal European Heart Journal Section Body Doc Link PMC2515885 Disease Relevance 0.77 Pain Relevance 0.11
These results define a new pharmacophore for C5a antagonist development and advance our understanding of ligand recognition and receptor activation of this G protein-coupled receptor.
Positive_regulation (activation) of protein-coupled receptor associated with antagonist
14) Confidence 0.34 Published 2004 Journal Mol. Pharmacol. Section Abstract Doc Link 15044616 Disease Relevance 0 Pain Relevance 0.39
Among downstream events after endothelin receptor activation, ET-1 causes EGF receptor transactivation, which is partly responsible for MAPK activation [13,14].


Positive_regulation (activation) of endothelin receptor
15) Confidence 0.32 Published 2004 Journal J Transl Med Section Body Doc Link PMC436068 Disease Relevance 0.58 Pain Relevance 0.13
These results indicate that the ET-1/ETAR axis could be targeted for antitumor therapy.
Positive_regulation (targeted) of ETAR
16) Confidence 0.32 Published 2004 Journal J Transl Med Section Body Doc Link PMC436068 Disease Relevance 1.94 Pain Relevance 0.13
However, the vasodilator effects of endothelial ETB activation are not enough to overcome the intense vasoconstrictor effect of ETA activation and the overall effect of ET-1 in most vascular beds is one of intense vasoconstriction (Seo et al 1994).
Positive_regulation (activation) of ETA associated with increased venous pressure under development
17) Confidence 0.28 Published 2008 Journal Drug design, development and therapy Section Body Doc Link PMC2761178 Disease Relevance 0.41 Pain Relevance 0
In studies of porcine eyes, ET-1 increases ocular blood flow at negligible doses and reduces it at higher ones, which is thought to occur secondary to activation of ETB and ETA receptors, respectively (Yao et al 1991).
Positive_regulation (activation) of ETA in blood
18) Confidence 0.27 Published 2008 Journal Clinical Ophthalmology (Auckland, N.Z.) Section Body Doc Link PMC2699797 Disease Relevance 0.77 Pain Relevance 0
We therefore tested the effects of ETAR activation on the TRPV1 mutant TRPV1-S800A.
Positive_regulation (activation) of ETAR
19) Confidence 0.24 Published 2007 Journal Mol Pain Section Body Doc Link PMC2206006 Disease Relevance 0 Pain Relevance 0.29
The results suggest that ET-1, through activation of the ETA receptor, is of importance for the regulation of the microcirculation in diabetic patients with micro-angiopathy.
Positive_regulation (activation) of ETA associated with vascular disease and diabetes mellitus
20) Confidence 0.24 Published 2008 Journal Vascular Health and Risk Management Section Body Doc Link PMC2605330 Disease Relevance 0.96 Pain Relevance 0.04

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