INT78178

Context Info Confidence 0.75 First Reported 1998 Last Reported 2009 Negated 0 Speculated 1 Reported most in Abstract Documents 21 Total Number 22 Disease Relevance 7.10 Pain Relevance 6.37

pigmentation (Ednrb) aging (Ednrb) plasma membrane (Ednrb) signal transducer activity (Ednrb)

Anatomy Link Frequency eyes 3 smooth muscle cells 3 brain 2 middle cerebral artery 1 fibroblasts 1 Ednrb (Rattus norvegicus)

Pain Link Frequency Relevance Heat antagonist 75 100.00 analgesia 7 100.00 Opioid 7 100.00 Morphine 28 99.84 nociceptor 2 99.52 mu opioid receptor 2 98.92 narcan 15 98.32 Pain 8 98.02 Analgesic 2 96.08 medulla 3 96.00

Disease Link Frequency Relevance Heat Pulmonary Hypertension 319 99.84 Middle Cerebral Artery Infarction 126 98.66 Reprotox - General 1 5 98.52 Pain 6 98.02 Increased Venous Pressure Under Development 53 98.00 Malignant Neoplastic Disease 1 97.76 Disease 74 97.64 Pulmonary Disease 6 96.48 Systemic Sclerosis 19 96.22 Injury 15 94.68

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

We also examined ETA and ETB mRNA expression by quantitative real-time polymerase chain reaction.

Spec (examined) Gene_expression (expression) of ETB mRNA

1) Confidence 0.75 Published 2004 Journal J. Cardiovasc. Pharmacol. Section Abstract Doc Link 15838338 Disease Relevance 0.18 Pain Relevance 0.09

As a result, the expressions of ETA and ETB receptors are reduced with both immunostaining and the mRNA levels in the left eye, in which endothelin-1 eyedrops were applied at 4 x 10(-5) M.

Gene_expression (expressions) of ETB in eye

2) Confidence 0.75 Published 2004 Journal J. Cardiovasc. Pharmacol. Section Abstract Doc Link 15838338 Disease Relevance 0.17 Pain Relevance 0.08

As an index to the action of endothelin- 1 eyedrops to the retina, the expressions of endothelin-A (ETA) and endothelin-B (ETB) receptors in the retina were compared in both eyes.

Gene_expression (expressions) of endothelin-B in eyes

3) Confidence 0.65 Published 2004 Journal J. Cardiovasc. Pharmacol. Section Abstract Doc Link 15838338 Disease Relevance 0.21 Pain Relevance 0.10

As an index to the action of endothelin- 1 eyedrops to the retina, the expressions of endothelin-A (ETA) and endothelin-B (ETB) receptors in the retina were compared in both eyes.

Gene_expression (expressions) of ETB in eyes

4) Confidence 0.58 Published 2004 Journal J. Cardiovasc. Pharmacol. Section Abstract Doc Link 15838338 Disease Relevance 0.21 Pain Relevance 0.10

In the control group, immunohistochemistry confirmed an enhanced expression of ETB receptor protein in the smooth muscle cells of the right MCA after transient MCAO.

Gene_expression (expression) of ETB receptor protein in smooth muscle cells associated with middle cerebral artery infarction

5) Confidence 0.46 Published 2007 Journal BMC Neurosci Section Body Doc Link PMC1770924 Disease Relevance 0.22 Pain Relevance 0.25

At 24 hours after transient middle cerebral artery occlusion (MCAO), the contractile endothelin B receptor mediated response and the endothelin B receptor protein expression were upregulated in the ipsilateral but not the contralateral middle cerebral artery.

Gene_expression (expression) of endothelin B receptor in middle cerebral artery associated with middle cerebral artery infarction

6) Confidence 0.46 Published 2007 Journal BMC Neurosci Section Abstract Doc Link PMC1770924 Disease Relevance 0.64 Pain Relevance 0.24

Moreover, immunohistochemistry showed enhanced expression of ETB receptor protein in the ipsilateral MCA of the control rats.

Gene_expression (expression) of ETB receptor protein

7) Confidence 0.46 Published 2007 Journal BMC Neurosci Section Body Doc Link PMC1770924 Disease Relevance 0.54 Pain Relevance 0.14

In males, exposure to endothelin-1 decreased mu opioid receptor expression without changing endothelin-A receptor or endothelin-B receptor expression in the hindpaw skin.

Gene_expression (expression) of endothelin-B receptor in skin associated with mu opioid receptor

8) Confidence 0.38 Published 2009 Journal Neurosci. Lett. Section Abstract Doc Link 19788914 Disease Relevance 0.06 Pain Relevance 1.18

Recent research investigating the role of vasoactive intestinal peptide (VIP) in rats has produced promising results.110 This study showed that ETA antagonists, ETB antagonists, and VIP all prevented the pulmonary vasoconstriction caused by ET1.

Gene_expression (antagonists) of ETB associated with antagonist and increased venous pressure under development

9) Confidence 0.36 Published 2009 Journal Vascular Health and Risk Management Section Body Doc Link PMC2697585 Disease Relevance 0.80 Pain Relevance 0.19

Anti-beta-endorphin IgG down-regulated ET-A receptor protein expression in the caudate (51%), but had no effect on the expression of mu, delta, kappa opioid, ET-B, CRH-1 and CRH-2 receptors in any brain region.

Gene_expression (expression) of ET-B in brain associated with opioid

10) Confidence 0.32 Published 2006 Journal Peptides Section Abstract Doc Link 16165252 Disease Relevance 0 Pain Relevance 0.51

The expression of phosphorylated ERK1/2 and Elk-1, and of endothelin ETA and ETB, angiotensin AT1, and 5-hydroxytryptamine 5-HT1B receptors were analyzed with immunohistochemistry using confocal microscopy in cerebral arteries, microvessels and in brain tissue.

Gene_expression (expression) of ETB in brain

11) Confidence 0.22 Published 2008 Journal BMC Neurosci Section Abstract Doc Link PMC2553085 Disease Relevance 0.44 Pain Relevance 0.08

We observed for the first time a significant increase in the expression of endothelin ETB, angiotensin AT1, and 5-hydroxytryptamine 5-HT1B receptors in smooth muscle cells not only in the ischemic MCA but also in smooth muscle cells of cerebral microvessels associated with the ischemic region (Fig. 6 and 7).

Gene_expression (expression) of ETB in smooth muscle cells

12) Confidence 0.22 Published 2008 Journal BMC Neurosci Section Body Doc Link PMC2553085 Disease Relevance 0.28 Pain Relevance 0

Double immunostaining for endothelin ETB, angiotensin AT1, and 5-hydroxytryptamine 5-HT1B receptors versus smooth muscle actin, expressed in the smooth muscle cells, revealed clear co-localization.

Gene_expression (expressed) of ETB in smooth muscle cells

13) Confidence 0.22 Published 2008 Journal BMC Neurosci Section Body Doc Link PMC2553085 Disease Relevance 0.23 Pain Relevance 0

Alterations in the distribution and number of ETA and ETB receptors in conditions such as PAH suggest that their roles in the disease state may differ from those in normal physiology.

Gene_expression (receptors) of ETB associated with pulmonary hypertension and disease

14) Confidence 0.13 Published 2008 Journal European Heart Journal Section Body Doc Link PMC2515885 Disease Relevance 0.97 Pain Relevance 0.06

In vitro data with skin fibroblasts suggested that targeting both the ETA and the ETB receptors is preferable in order to block collagen type I and III production.54 However, subsequent in vitro data using lung fibroblasts indicate that ET-1 induces collagen matrix contraction through the ETA receptor, but not the ETB receptor.55 Furthermore, while there is evidence that ETB receptors are linked to collagen production in vitro, in vivo animal data with ETA antagonists have shown that they effectively block the accumulation of collagen I, III, and IV,56 normalize pro-collagen I and III mRNA,49 and abolish the effect of ET-1 on pro-collagen metabolism.57 Likewise, although there is evidence that under certain conditions ET-1 can act as a mitogen in vitro through both ETA- and ETB-receptor activation,58 ETB receptors have been shown to inhibit vascular SMC proliferation in vivo.59 It has been suggested that ETB receptors may be up-regulated on SMCs and fibroblasts in certain disease states such as scleroderma lung disease.60 However, the spatial distribution of these receptors among different cell types within the lung microcirculation remains unclear, as does the significance of any increased ETB-receptor expression in PAH.

Gene_expression (expression) of ETB-receptor in fibroblasts associated with pulmonary hypertension, pulmonary disease, antagonist, systemic sclerosis and disease

15) Confidence 0.12 Published 2008 Journal European Heart Journal Section Body Doc Link PMC2515885 Disease Relevance 0.57 Pain Relevance 0.07

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

Gene_expression (selectivity) of ETB

16) Confidence 0.12 Published 2008 Journal European Heart Journal Section Body Doc Link PMC2515885 Disease Relevance 0.36 Pain Relevance 0.10

While it is able to trigger pain through its actions on endothelin-A (ET(A)) receptors of local nociceptors, it can coincidentally produce analgesia through endothelin-B (ET(B)) receptors.

Gene_expression (produce) of endothelin-B in nociceptors associated with pain, nociceptor and analgesia

17) Confidence 0.09 Published 2003 Journal Nat. Med. Section Abstract Doc Link 12847519 Disease Relevance 0.62 Pain Relevance 0.93

Two endothelin receptors, ET-A and ET-B are found in normal prostate tissue.

Gene_expression (found) of ET-B

18) Confidence 0.02 Published 2002 Journal Invest New Drugs Section Abstract Doc Link 12099577 Disease Relevance 0.57 Pain Relevance 0

Whereas ETA receptor mRNA expression increased 2-fold at 6 h and 4-fold at 96 h, ETB receptor mRNA expression remained unchanged.

Gene_expression (expression) of ETB receptor mRNA

19) Confidence 0.02 Published 2004 Journal Pediatr. Res. Section Abstract Doc Link 14605251 Disease Relevance 0 Pain Relevance 0.56

Naloxone caused a progressive decrease in ETA receptor mRNA expression at 6 h through 96 h and a 2-fold increase in ETB receptor mRNA expression at 48 and 96 h.

Gene_expression (expression) of ETB receptor mRNA associated with narcan

20) Confidence 0.02 Published 2004 Journal Pediatr. Res. Section Abstract Doc Link 14605251 Disease Relevance 0 Pain Relevance 0.54

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