Disease relevance of Ednrb

• Renal endothelin receptor type B upregulation in rats with low or high renin hypertension [1].
• These data strongly suggest that ET, acting through ETB receptors, may play an important role in mediating neurogenic inflammation in the meninges of rats [2].
• Pharmacology of a non-selective ETA and ETB receptor antagonist, TAK-044 and the inhibition of myocardial infarct size in rats [3].
• These data indicate that ET-1 interacts with both ETA and ETB receptors to elicit calcium transients in UMR-106 osteoblastic osteosarcoma cells [4].
• The ETA receptor density was significantly elevated, whereas the density of the ETB receptor was decreased in Morris hepatoma 7777 [5].

High impact information on Ednrb

• Ednrb-deficient gut neural crest stem cells (NCSCs) were reduced to 40% of wild-type levels by embryonic day 12.5 (E12.5), but no further depletion of NCSCs was subsequently observed [6].
• Loss of Endothelin-3/Endothelin receptor B (EDNRB) signaling leads to aganglionosis of the distal gut (Hirschsprung's disease), but it is unclear whether it is required primarily for neural crest progenitor maintenance or migration [6].
• The DbetaH-EDNRB transgene compensates for deficient endogenous EDNRB in these rats and prevents the intestinal defect [7].
• We used the human dopamine-beta-hydroxylase (DbetaH) promoter to direct transgenic expression of EDNRB to colonizing ENS precursors in the sl/sl rat [7].
• The transgene has no effect on coat color spotting, indicating the critical time for EDNRB expression in enteric nervous system development begins after separation of the melanocyte lineage from the ENS lineage and their common precursor [7].

Chemical compound and disease context of Ednrb

• 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) [8].
• Experiments were designed to determine whether clofibrate reduces hypertension associated with chronic ETB receptor blockade [9].
• Endothelin-1 is involved in norepinephrine-induced ventricular hypertrophy in vivo. Acute effects of bosentan, an orally active, mixed endothelin ETA and ETB receptor antagonist [10].
• These data indicate that glomerular ET-1 and ETB receptor expression in PAN nephrosis in increased at the mRNA level and that methylprednisolone treatment results in an attenuated increase [11].
• The aim of this study was to investigate the effects of tezosentan, a non-selective ETA and ETB receptor antagonist, in LPS challenged rats with cirrhosis [12].

Biological context of Ednrb

• ET-2, ET-3, and IRL 1620, a highly selective agonist of ETB receptor, elicit [Ca2+]i increases, though with dissimilar potencies and kinetics [13].
• Endothelin-1 has dual vasoactive effects, mediating vasoconstriction via ETA receptor activation of vascular smooth muscle cells and vasorelaxation via ETB receptor activation of endothelial cells [14].
• 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 [15].
• We describe here a sex difference in endothelin action in hepatocytes because, in female rats, 80% of the ET receptors are of ETB type and, accordingly, activation of glycogenolysis is an ETB-mediated process (EC50 = 0.03 pM) [15].
• Low levels of plasma ET-1 are rapidly cleared, mainly in the pulmonary circulation, through a low-capacity saturable ETB receptor-linked mechanism [16].

Anatomical context of Ednrb

• Mesangial cells can be a source of NO coupled to ETB receptor activation in glomerulus [17].
• 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 [18].
• Moreover, lipocytes expressed both ETA and ETB receptors [18].
• Dual control of seminiferous tubule contractility mediated by ETA and ETB endothelin receptor subtypes [13].
• We conclude that the calcium signal provoked by endothelins in hepatocyte is not only consecutive to activation of phospholipase C but also to inhibition of the plasma membrane calcium pump, each effector being coupled to ETB receptors by different G proteins, Gq, and Gs [15].

Associations of Ednrb with chemical compounds

• Endothelin (ET)-3 stimulates cyclic guanosine 3',5'-monophosphate production via ETB receptor by producing nitric oxide in isolated rat glomerulus, and in cultured rat mesangial cells [17].
• 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 [19].
• However, in the presence of U-73122, the selective stimulation of ETB receptors induced the mobilization of a thapsigargin-sensitive and inositol phosphate-independent intracellular Ca2+ pool [13].
• To identify the nature of the guanine nucleotide regulatory proteins (G protein(s)) coupling ETB receptors to each effector, we used antibodies against the COOH terminus of different G protein alpha subunits [15].
• 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 [20].

Physical interactions of Ednrb

• Although it is commonly accepted that endothelin-1 binding to endothelial cell ETB receptors stimulates nitric oxide (NO) synthesis and subsequent smooth muscle relaxation, the signaling pathways downstream of ETB receptor activation are unknown [14].
• The three monoiodo ET-3 derivatives bound to recombinant rat ETB receptors with a pM affinity [21].
• Quantitative autoradiography showed that ET-1[1-21] displaced both [(125)I]PD-151242 binding to ETA receptors and [(125)I]BQ-3020 binding to ETB receptors in both rat ZG and adrenal medulla, while ET-1[1-31] displaced only [(125)I]BQ-3020 binding [22].

Regulatory relationships of Ednrb

• We conclude that ET-3 stimulates NO-induced cGMP generation through ETB receptor in glomerulus [17].
• The ETB receptor stimulates activation of the extracellular regulated kinase 2 (ERK2), which is thought to be required for proliferation of ASM cells [23].
• These results suggest that activation of brain ETB receptors induced GDNF and BDNF expression in astrocytes [24].
• Treatment with bosentan or ET-A receptor antagonist largely prevented the colitis-induced reduction in blood flow and tissue injury whereas ET-B receptor antagonist did not attenuate tissue injury or reductions in blood flow [25].
• Hypoxia-induced reactive oxygen species downregulate ETB receptor-mediated contraction of rat pulmonary arteries [26].

Other interactions of Ednrb

• From these results, mesangial ETB receptor may work to counteract the vasoconstrictive effect of endothelin caused via ETA receptor in glomerulus [17].
• ETB receptor agonist IRL 1620 produced cGMP in a dose-dependent manner, mimicking the effect of ET-3 [17].
• Functional link between ETB receptors and eNOS maintain tissue oxygenation in the normal liver [27].
• Therefore, chronic PPAR-alpha agonist treatment reduces salt-dependent hypertension produced by ETB receptor blockade in male and female Sprague-Dawley rats [9].
• Taken together, the data elucidate a G-protein-coupled receptor signaling pathway for ETB receptor-mediated NO production and call attention to the absolute requirement for heterotrimeric G-protein betagamma subunits in this cascade [14].

Analytical, diagnostic and therapeutic context of Ednrb

• 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 [19].
• A parallel but marked increase in ETA and ETB receptor mRNAs compared with preproET-1 and -3 messages was observed after angioplasty [28].
• Retrograde perfusion suggests that ETB receptors are located arterially whereas ETA receptors are predominantly venous in distribution.(ABSTRACT TRUNCATED AT 250 WORDS)[29]
• The most likely explanation is upregulation of functional ETA receptors after I/R because ETB-receptor stimulation did not cause coronary constriction in this preparation [30].
• Although mRNA transcripts specific for both ETA and ETB receptors were found by RT-PCR, the ETA mRNA was more abundant [31].

References