Disease relevance of ETB

• These studies were designed to test the hypothesis that experimental hypercholesterolemia is characterized by a differentially altered coronary contractile response to ETA- and ETB-receptor stimulation, in vitro [1].
• The amino acid sequences of these four toxins were homologous to the earlier described exfoliative toxins SHETB from S. hyicus and ETA, ETB, and ETD from Staphylococcus aureus [2].
• Taken together, our present observations suggest that ET(s) influences pulmonary functions by constricting airway smooth muscle via ETB receptors during the immediate asthmatic response and by modulating pulmonary inflammation via ETA receptors during the late asthmatic response, respectively [3].
• Plasma ET-1 increased from 1.50 and 1.17 ng/L at baseline to 2.07 and 3.18 ng/L at the end of hypoxemia in the ETA and ETB groups respectively [4].
• The vasoconstriction induced by the ETB receptor agonist [Ala 1,3,11,15] ET-1 or serotonin was not significantly affected by ischemia/reperfusion [5].

High impact information on ETB

• Two endothelin receptors (ETA and ETB) expressed on circular smooth muscle cells of guinea pig cecum [6].
• CONCLUSIONS: The results show a direct contractile effect of ETs on circular smooth muscle of guinea pig cecum and the presence of both ETA- and ETB-receptor subtypes [6].
• Endothelin-1 (ET-1) is a 21-amino acid peptide hormone released from myocardial and endothelial cells, whose receptors (both ETA and ETB are expressed in the myocardium [7].
• The effect of ET-1 appeared to be mediated by an ETA receptor, because it was prevented by FR139317, an ETA-selective antagonist (1 mumol/L, n = 4), and sarafotoxin s6c, an ETB-selective agonist (100 nmol/L, n = 4), could not inhibit the ISO-enhanced IK [7].
• These studies demonstrate that experimental hypercholesterolemia is characterized by enhanced coronary vasoconstriction to endothelins in vitro, the mechanism of which is mediated mainly through the ETB receptor [1].

Chemical compound and disease context of ETB

• Hypoxia (0% O2) caused a late-phase, endothelium-dependent contractile response that was not inhibited by the endothelin (ET)A-receptor antagonist BQ-123 (10(-6) M), by the ETB-receptor antagonist BQ-788 (10(-7) M), or by their combination [8].
• Endothelin (ET)-1, a potent vasoconstrictor and mitogen, acts through ETA and ETB receptors and may be involved in the pathogenesis of persistent pulmonary hypertension of the newborn [9].

Biological context of ETB

• Studies were conducted to determine whether endothelin (ET) ETA and ETB receptor protein and mRNA expression is developmentally regulated in the postnatal swine mesenteric circulation [10].
• This finding combined with the observed relative potencies of the peptides (IRL 1620 > ET-1 = ET-3) suggests that pulmonary vasodilatation was mediated by activation of the non-selective ETB receptor [11].
• In vitro constrictive responses of isolated tracheas and bronchi to ET1 were inhibited mainly by BQ123 and BQ788, respectively, which suggested that distribution of ETA and ETB receptors for bronchoconstriction are topographically distinct along airways [3].
• The binding affinity of LLC-PK1 cells was about 10,000 times higher for the ETB antagonist BQ-788 [N-cis-2,6-dimethyl-piperidinocarbonyl-L-tau-metylleucyl-D-+ ++Nin- methoxycarbonyltryptophanyl-D-norleucine] (IC50, 1.3 nM) than for the ETA antagonist BQ-123 [cyclo-(D-Trp-D-Asp-Pro-D-Val-Leu)] (IC50, 14 microM) [12].
• Direct activation of ETA expressed on the basal cells caused enhancement of their growth, whereas that of ETB expressed on the ciliated columnar cells caused suppression of the basal cell growth [13].

Anatomical context of ETB

• Thus, the ETB receptor has a role in regulation of coronary artery tone in both the steady-state and pathophysiological states [1].
• Influence of regional differences in ETA and ETB receptor subtype proportions on endothelin-1-induced contractions in porcine isolated trachea and bronchus [14].
• These experiments indicated the presence of functioning ETA receptors in addition to ETB receptors in endothelial cells in situ [15].
• Therefore, the ETB receptors in LLC-PK1 cells couple to the two types of signal transduction cascades to reduce cAMP production and stimulate cGMP production via distinct G-proteins [12].
• Furthermore, blockade of either ETA or ETB compromised the epithelial cell layer formation under the air-interphase culture, which indicates the dependence of tracheal epithelial remodeling on a balance between the positive and negative effects of ET-1 on the basal cell growth [13].

Associations of ETB with chemical compounds

• The coronary vasoconstrictor effects of endothelins, mediated by both endothelin ETA and ETB receptors, may be differentially altered in pathophysiological states associated with endothelial dysfunction and elevated endothelin levels [1].
• Incubation of arteries from hypercholesterolemic pigs with BQ-788 (ETB-receptor antagonist), but not FR-139317 (ETA-receptor antagonist), altered the contractile response to ET-1 at 10(-10) mol/L [1].
• The ETB selective antagonist BQ-788 (100 nM) shifted S6c responses rightward but produced no change in ET-1 responses [16].
• 4. In trachea, endothelin-1 induced contractions were not significantly inhibited by either the ETA receptor-selective antagonist, BQ-123 (3 microM) or the ETB receptor-selective antagonist, BQ-788 (1 microM) [14].
• 3. In the same perfused model, the selective ETB agonist, IRL 1620 (50 nM), stimulated the release of thromboxane A2, but not prostacyclin [17].

Other interactions of ETB

• Losartan therapy was associated with persistent overexpressions of ANG II, AT2, ET-1, ETB, and angiopoietin-1 and with a return to normal of the BMPR-2 expression [18].
• We conclude that ETB receptors play a central role in mediating ET-1-induced vasoconstriction in pig skin, and the mechanism probably involves L-type Ca2+ channels, PLC, and PKC [19].

Analytical, diagnostic and therapeutic context of ETB

• Abundant polymerase chain reaction products for both the ETA and the ETB message were observed [6].
• RT-PCR for the pig ETB receptor revealed that endothelial cells of the aortic valve express ETB receptor messenger RNA (mRNA).(ABSTRACT TRUNCATED AT 250 WORDS)[15]
• However, there is little information on the effects of dual ETA/ETB receptor blockers, such as bosentan, on neointimal proliferation following experimental coronary angioplasty [20].
• This study was designed to investigate whether or not a novel nonselective endothelin A/B (ETA/ETB) receptor antagonist (TAK-044) provides hepatoprotection during porcine liver transplantation [21].
• Intra-arterial infusion of the ETA/B receptor agonist ET-1, the ETB receptor agonists sarafotoxin 6C (S6c) and BQ-3020, or the thromboxane A2 mimetic U-46619 (n = 4 or 5) caused a concentration-dependent skin vasoconstriction [19].

References