Disease relevance of Ednra

• In addition, the tissue concentration of endothelin and endothelin 1 messenger RNA (mRNA) and the effect of an endothelin A receptor antagonist on arterial and portal pressure were assessed in cirrhotic rats with ascites and control rats [1].
• The role of ETB receptors in mediating inflammation was evidenced by the lack of efficacy of a selective ETA receptor antagonist, in contrast to the full efficacy of a selective ETB receptor antagonist, for preventing neurogenic inflammation induced by unilateral stimulation of the trigeminal ganglion [2].
• The results suggest that endothelins increase cAMP levels via ETA receptor activation interacting with the pertussis toxin-insensitive G-protein, in which PGE2 production is involved in the rat anterior pituitary, whereas endothelins lack these effects in the intermediate-posterior pituitary [3].
• The ETA receptor density was significantly elevated, whereas the density of the ETB receptor was decreased in Morris hepatoma 7777 [4].
• These data indicate that ET-1 interacts with both ETA and ETB receptors to elicit calcium transients in UMR-106 osteoblastic osteosarcoma cells [5].

High impact information on Ednra

• Indeed, blockade of ETA endothelin receptors with BQ-610 (1 microM), similar to removal of the endothelium and alpha5 integrin blockade, inhibited the vasoconstriction [6].
• Interestingly, ET-3-induced skeletal alpha-actin gene expression and [3H]leucine incorporation were inhibited by a synthetic ETA receptor antagonist (BQ123) as well as by antisense oligonucleotides against peproET-1 mRNA [7].
• Stellate cells possess abundant endothelin (ET) receptors (ETA/B) and, therefore, are subject to the effects of ET-1 and 3 [8].
• Furthermore, the mixed ETA/B receptor antagonist, bosentan, blocked this process [8].
• Since ETA receptor mRNA is increased under hyperosmolar conditions, we conclude that ET receptor downregulation is the consequence of either decreased translation of message, increased degradation of receptor peptide, or increased internalization of specific receptor sites [9].

Chemical compound and disease context of Ednra

• Administration of bacterial lipopolysaccharide (LPS) caused profound hypotension, increased heart rate and death, and these effects were blocked by a nonselective ETA/ETB receptor antagonist (TAK044), but not by an ETA selective antagonist (BQ123) [10].
• In addition, our recent experiments have demonstrated that administration of BQ-123, a selective ET-AR antagonist, abolished the pulmonary vasoconstrictor response to acute (0-90 min) and chronic (2 weeks) hypoxia, further suggesting that ET-1 plays an important role in the pathogenesis of hypoxia-induced pulmonary hypertension in the rat [11].
• Blockade of ET A and B receptors by bosentan did not inhibit the occurrence of nephrotic syndrome [12].
• Pretreatment with molsidomine or blockade of ETA receptors by BQ 610 can unmask the positive inotropy of ET-1 by preventing ET-induced myocardial ischemia [13].
• Recent studies demonstrated that ETA receptors regulate cardiac MMP activity and fibrosis in DOCA-salt hypertension [14].

Biological context of Ednra

• Endothelin A receptor blockade was not associated with significant changes in arterial and portal pressure in any group of animals [1].
• The ET binding site therefore had the characteristics of an ETA-like receptor [15].
• We have demonstrated in liver from male rats that both endothelin A (ETA) and ETB receptors coexist in equal proportion and that ETA receptors mediate a calcium-dependent activation of glycogenolysis [16].
• The data indicate that in rat myometrium the ETA receptor is coupled, via two distinct G proteins, to two main signal transduction cascades, which both undergo rapid desensitization [17].
• Hence, ETA receptor antagonists should attenuate ET-mediated vasoconstriction [18].

Anatomical context of Ednra

• The mRNA for ETB receptor, but not for ETA receptor, was detectable in sinusoidal endothelial cells and Kupffer cells; neither mRNA was detectable in hepatocytes [19].
• Moreover, lipocytes expressed both ETA and ETB receptors [19].
• These results demonstrate that ANF and BNP secretion by atrial myocytes is enhanced by ET via binding to an ETA-like receptor [15].
• The ETA receptor is a seven-transmembrane G-protein-coupled receptor whose precise subcellular localization in cardiac muscle is unknown [20].
• These results suggest that ET can activate MAP kinases through both ET receptors but act exclusively through ETA in glomerular mesangial cells [21].

Associations of Ednra with chemical compounds

• METHODS: Male Sprague-Dawley rats were continuously infused with 2.5 mL/h of saline, 0.8 mg . kg-1 . h-1 of lipopolysaccharide (LPS), 3 mg . kg-1 . h-1 of BQ-485, an endothelin A-receptor antagonist, or LPS plus BQ-485 for 7 hours [22].
• Secretion of the natriuretic peptides was blocked by BQ-123, an ETA-receptor antagonist, but was not affected by either IRL-1620 or [Ala1,3,11,15]ET-1, two ETB-receptor agonists [15].
• Regulation of endothelin-A receptor sensitivity by cyclic adenosine monophosphate in rat hepatic stellate cells [23].
• Rats were fed a K(+)-deficient diet alone (LC) or with an ETA-selective antagonist ABT-627 (LA) or an ETB-selective antagonist A-192621 (LB) for 8 wk [24].
• These increases were followed by decreased expression of ECE-1, ET A-type receptor, and ET B-type receptor mRNA at 6 h after injection, and serum creatinine levels were increased at 24 h after CsA injection [25].

Physical interactions of Ednra

• Furthermore, ET-3 binding in the inner medulla could be blocked with an ETA receptor antagonist in sl/sl rats but not in tissue from sl/+ rats [26].
• Collectively, these findings suggest that ETs can regulate vascular tone in the in situ perfused rat adrenals via both PKC-coupled ETA and NOS-coupled ETB receptors, the activation of which evokes vasoconstriction and vasodilation, respectively [27].

Regulatory relationships of Ednra

• ETA blockade significantly ameliorated all parameters for renal injury in the cortex without suppressing local ET-1 and ETA expression [24].
• Moreover, the LPS inhibitory effect of on mucin synthesis was blocked by ETA receptor antagonist, BQ610, but not by ETB receptor antagonist, BQ788 [28].
• Although ET-3 also activates ETA receptors in smooth muscle to induce contraction, this effect is overcome by the relaxant effect mediated by ETB receptors [29].
• Thus, ET-1 contracts rat pulmonary artery and aorta predominantly via ETA receptors (responses blocked by BQ-123) and functional ETB receptors are unlikely to be present (no responses to IRL 1620) [30].
• Endothelin-1 inhibits secretin-stimulated ductal secretion by interacting with ETA receptors on large cholangiocytes [31].

Other interactions of Ednra

• From these results, mesangial ETB receptor may work to counteract the vasoconstrictive effect of endothelin caused via ETA receptor in glomerulus [32].
• ETA receptor antagonist BQ123-Na did not inhibit ET-3- or IRL 1620-stimulated cGMP generation [32].
• Endothelin stimulates mitogen-activated protein kinase activity in mesangial cells through ETA [21].
• Endothelin-1 did not mediate the cardiac hypertrophic effect of AngII through ETA receptors [33].
• Endothelin A receptor blockade decreases expression of growth factors and collagen and improves matrix metalloproteinase-2 activity in kidneys from stroke-prone spontaneously hypertensive rats [34].

Analytical, diagnostic and therapeutic context of Ednra

• The levels of ETA receptor mRNA were elevated 29.3-fold (P < .001) and 24.3-fold (P < .01) at 3 and 7 days, respectively, after angioplasty [35].
• Northern blot analysis of both ETA- and ETB-receptor mRNAs allowed only the detection of the former, indicating that the ETB receptor may be expressed in very small amounts [15].
• Moreover, the ETA receptor and downstream effector phospholipase C-beta 1 were co-localized within T-tubules using standard immunofluorescence techniques, and protein kinase C (PKC)-epsilon-enhanced green fluorescent protein bound reversibly to T-tubules upon activation [20].
• Retrograde perfusion suggests that ETB receptors are located arterially whereas ETA receptors are predominantly venous in distribution.(ABSTRACT TRUNCATED AT 250 WORDS)[36]
• Castration does not cause significant changes in the pharmacological properties of prostatic ET receptors, i.e., the predominance of ETA receptors in either region of the prostate, or the expression of ETA receptor subtype mRNA in the ventral region of the castrated rat prostate [37].

References