Journal articles: 'Endothelin receptor – type B'

1

Pollock, David M., and Markus P. Schneider. "Clarifying Endothelin Type B Receptor Function." Hypertension 48, no. 2 (August 2006): 211–12. http://dx.doi.org/10.1161/01.hyp.0000229908.62191.6e.

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Zhang, Junlan, Yiqun Ling, Liping Tang, Bao Luo, David M. Pollock, and Michael B. Fallon. "Attenuation of experimental hepatopulmonary syndrome in endothelin B receptor-deficient rats." American Journal of Physiology-Gastrointestinal and Liver Physiology 296, no. 4 (April 2009): G704—G708. http://dx.doi.org/10.1152/ajpgi.90627.2008.

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Experimental hepatopulmonary syndrome (HPS) after common bile duct ligation (CBDL) in rat is accompanied by increased lung vascular endothelial endothelin B (ETB) receptor expression and increased circulating levels of endothelin-1 (ET-1). The onset of HPS is hypothesized to be triggered by ET-1/ETB receptor activation of endothelial nitric oxide synthase (eNOS)-derived NO production in the pulmonary endothelium. However, whether functional pulmonary vascular ETB receptors are required for the development of experimental HPS is not defined. We evaluated the effects of vascular ETB receptor deficiency on the development of experimental HPS. The molecular and physiological alterations of HPS were compared in 2-wk CBDL wild-type and ETB receptor-deficient (transgenic sl/sl) rats. Relative to wild-type rats, basal hepatic and plasma ET-1 levels were elevated in sl/sl controls although, unlike wild-type animals circulating ET-1 levels, did not increase further after CBDL in sl/sl animals. In contrast to wild-type animals, ETB receptor-deficient rats did not develop increased Akt and eNOS expression and activation and did not develop gas exchange abnormalities of HPS after CBDL. There was a similar degree of pulmonary intravascular monocyte accumulation in both 2-wk CBDL sl/sl and wild-type animals. In conclusion, ETB receptor deficiency inhibits lung Akt/eNOS activation and prevents the onset of experimental HPS after CBDL. This effect is independent of inhibition of pulmonary intravascular monocyte accumulation. These results demonstrate that ET-1/ETB receptor signaling plays a key role in the initiation of experimental HPS.

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Seccia, Teresa M., and Lorenzo A. Calò. "Endothelin-1-induced endothelial mesenchimal transition via endothelin type B receptor stimulation." Journal of Hypertension 35, no. 6 (June 2017): 1329–30. http://dx.doi.org/10.1097/hjh.0000000000001344.

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Lau, Denise, Katalin Szöcs, Anna Klinke, Tanja Rudolph, Volker Rudolph, Thomas Streichert, Stefan Blankenberg, and Stephan Baldus. "Myeloperoxidase upregulates endothelin receptor type B expression." Journal of Molecular and Cellular Cardiology 69 (April 2014): 76–82. http://dx.doi.org/10.1016/j.yjmcc.2013.12.007.

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5

Okamoto, Yasuo, Haruaki Ninomiya, and Tomoh Masaki. "Posttranslational Modifications of Endothelin Receptor Type B." Trends in Cardiovascular Medicine 8, no. 8 (November 1998): 327–29. http://dx.doi.org/10.1016/s1050-1738(98)00027-9.

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Lau, Denise, Katalin Szöcs, Anna Klinke, and Stephan Baldus. "Myeloperoxidase Modulates Endothelin Receptor Type B Expression." Free Radical Biology and Medicine 49 (January 2010): S145. http://dx.doi.org/10.1016/j.freeradbiomed.2010.10.404.

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Terada, Koji, Takahiro Horinouchi, Tsunehito Higashi, Prabha Nepal, and Soichi Miwa. "Ubiquitination-regulated receptor trafficking of endothelin type A and type B receptors." Folia Pharmacologica Japonica 145, no. 1 (2015): 4–9. http://dx.doi.org/10.1254/fpj.145.4.

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Okuta, Akiko, Kazutoshi Tani, Shoko Nishimura, Yoshinori Fujiyoshi, and Tomoko Doi. "Thermostabilization of the Human Endothelin Type B Receptor." Journal of Molecular Biology 428, no. 11 (June 2016): 2265–74. http://dx.doi.org/10.1016/j.jmb.2016.03.024.

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9

Chiou, W. J., S. R. Magnuson, D. Dixon, S. Sundy, T. J. Opgenorth, and J. R. Wu-wong. "Dissociation Characteristics of Endothelin Receptor Agonists and Antagonists in Cloned Human Type-B Endothelin Receptor." Endothelium 5, no. 3 (January 1997): 179–89. http://dx.doi.org/10.3109/10623329709053397.

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Mazaki, Yuichi, Tsunehito Higashi, Yasuhito Onodera, Jin-Min Nam, Ari Hashimoto, Shigeru Hashimoto, Takahiro Horinouchi, and Soichi Miwa. "GRP78 promotes ERK activation through endothelin type B receptor." Proceedings for Annual Meeting of The Japanese Pharmacological Society 92 (2019): 1—P—110. http://dx.doi.org/10.1254/jpssuppl.92.0_1-p-110.

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11

Taura, Daisuke, Kazuhiro Nakao, Yasuaki Nakagawa, Hideyuki Kinoshita, Masakatsu Sone, and Kazuwa Nakao. "C-type natriuretic peptide (CNP)/guanylate cyclase B (GC-B) system and endothelin-1(ET-1)/ET receptor A and B system in human vasculature." Canadian Journal of Physiology and Pharmacology 98, no. 9 (September 2020): 611–17. http://dx.doi.org/10.1139/cjpp-2019-0686.

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To assess the physiological and clinical implications of the C-type natriuretic peptide (CNP)/guanylyl cyclase B (GC-B) system in the human vasculature, we have examined gene expressions of CNP and its receptor, GC-B, in human vascular endothelial cells (ECs) and smooth muscle cells (SMCs) and have also compared the endothelin-1(ET-1)/endothelin receptor-A (ETR-A) and endothelin receptor-B (ETR-B) system in human aortic ECs (HAECs) and vascular SMCs (HSMCs) in vitro. We also examined these gene expressions in human embryonic stem (ES)/induced pluripotent stem cell (iPS)-derived ECs and mural cells (MCs). A little but significant amount of mRNA encoding CNP was detected in both human ES-derived ECs and HAECs. A substantial amount of GC-B was expressed in both ECs (iPS-derived ECs and HAECs) and SMCs (iPS-derived MCs and HSMCs). ET-1 was expressed solely in ECs. ETR-A was expressed in SMCs, while ETR-B was expressed in ECs. These results indicate the existence of a vascular CNP/GC-B system in the human vascular wall, indicating the evidence for clinical implication of the CNP/GC-B system in concert with the ET-1/ETR-A and ETR-B system in the human vasculature.

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12

Katakam, Prasad Venkateswera Gurunath, Ferenc Domoki, Laura Lenti, Tamás Gáspár, Adam Institoris, James Andy Snipes, and David William Busija. "Cerebrovascular Responses to Insulin in Rats." Journal of Cerebral Blood Flow & Metabolism 29, no. 12 (September 2, 2009): 1955–67. http://dx.doi.org/10.1038/jcbfm.2009.177.

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Effects of insulin on cerebral arteries have never been examined. Therefore, we determined cerebrovascular actions of insulin in rats. Both PCR and immunoblot studies identified insulin receptor expression in cerebral arteries and in cultured cerebral microvascular endothelial cells (CMVECs). Diameter measurements (% change) of isolated rat cerebral arteries showed a biphasic dose response to insulin with an initial vasoconstriction at 0.1 ng/mL (−9.7%±1.6%), followed by vasodilation at 1 to 100 ng/mL (31.9%±1.4%). Insulin also increased cortical blood flow in vivo (30%±8% at 120 ng/mL) when applied topically. Removal of reactive oxygen species (ROS) abolished the vasoconstriction to insulin. Endothelial denudation, inhibition of K+ channels, and nitric oxide (NO) synthase, all diminished insulin-induced vasodilation. Inhibition of cytochrome P450 enhanced vasodilation in endothelium-intact arteries, but promoted vasoconstriction after endothelial denudation. Inhibition of cyclooxygenase abolished vasoconstriction and enhanced vasodilation to insulin in all arteries. Inhibition of endothelin type A receptors enhanced vasodilation, whereas endothelin type B receptor blockade diminished vasodilation. Insulin treatment in vitro increased Akt phosphorylation in cerebral arteries and CMVECs. Fluorescence studies of CMVECs showed that insulin increased intracellular calcium and enhanced the generation of NO and ROS. Thus, cerebrovascular responses to insulin were mediated by complex mechanisms originating in both the endothelium and smooth muscle.

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13

Ivy, D. Dunbar, Masashi Yanagisawa, Cheryl E. Gariepy, Sarah A. Gebb, Kelley L. Colvin, and Ivan F. McMurtry. "Exaggerated hypoxic pulmonary hypertension in endothelin B receptor-deficient rats." American Journal of Physiology-Lung Cellular and Molecular Physiology 282, no. 4 (April 1, 2002): L703—L712. http://dx.doi.org/10.1152/ajplung.00272.2001.

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Mechanisms by which endothelin (ET)-1 mediates chronic pulmonary hypertension remain incompletely understood. Although activation of the ET type A (ETA) receptor causes vasoconstriction, stimulation of ET type B (ETB) receptors can elicit vasodilation or vasoconstriction. We hypothesized that the ETB receptor attenuates the development of hypoxic pulmonary hypertension and studied a genetic rat model of ETB receptor deficiency (transgenic sl/sl). After 3 wk of severe hypoxia, the transgenic sl/sl pulmonary vasculature lacked expression of mRNA for the ETB receptor and developed exaggerated pulmonary hypertension that was characterized by elevated pulmonary arterial pressure, diminished cardiac output, and increased total pulmonary resistance. Plasma ET-1 was fivefold higher in transgenic sl/sl rats than in transgenic controls. Although mRNA for prepro-ET-1 was not different, mRNA for ET-converting enzyme-1 was higher in transgenic sl/sl than in transgenic control lungs. Hypertensive lungs of sl/sl rats also produced less nitric oxide metabolites and 6-ketoprostaglandin F1α, a metabolite of prostacyclin, than transgenic controls. These findings suggest that the ETB receptor plays a protective role in the pulmonary hypertensive response to chronic hypoxia.

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14

Bugaj, Vladislav, Elena Mironova, Donald E. Kohan, and James D. Stockand. "Collecting duct-specific endothelin B receptor knockout increases ENaC activity." American Journal of Physiology-Cell Physiology 302, no. 1 (January 2012): C188—C194. http://dx.doi.org/10.1152/ajpcell.00301.2011.

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Collecting duct (CD)-derived endothelin-1 (ET-1) acting via endothelin B (ETB) receptors promotes Na+ excretion. Compromise of ET-1 signaling or ETB receptors in the CD cause sodium retention and increase blood pressure. Activity of the epithelial Na+ channel (ENaC) is limiting for Na+ reabsorption in the CD. To test for ETB receptor regulation of ENaC, we combined patch-clamp electrophysiology with CD-specific knockout (KO) of endothelin receptors. We also tested how ET-1 signaling via specific endothelin receptors influences ENaC activity under differing dietary Na+ regimens. ET-1 significantly decreased ENaC open probability in CD isolated from wild-type (WT) and CD ETA KO mice but not CD ETB KO and CD ETA/B KO mice. ENaC activity in WT and CD ETA but not CD ETB and CD ETA/B KO mice was inversely related to dietary Na+ intake. ENaC activity in CD ETB and CD ETA/B KO mice tended to be elevated under all dietary Na+ regimens compared with WT and CD ETA KO mice, reaching significance with high (2%) Na+ feeding. These results show that the bulk of ET-1 inhibition of ENaC activity is mediated by the ETB receptor. In addition, they could explain the Na+ retention and elevated blood pressure observed in CD ET-1 KO, CD ETB KO, and CD ETA/B KO mice consistent with ENaC regulation by ET-1 via ETB receptors contributing to the antihypertensive and natriuretic effects of the local endothelin system in the mammalian CD.

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15

Rivera-Gonzalez, Osvaldo J., Malgorzata Kasztan, Jermaine G. Johnston, Kelly A. Hyndman, and Joshua S. Speed. "Loss of endothelin type B receptor function improves insulin sensitivity in rats." Canadian Journal of Physiology and Pharmacology 98, no. 9 (September 2020): 604–10. http://dx.doi.org/10.1139/cjpp-2019-0666.

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High salt intake (HS) is associated with obesity and insulin resistance. ET-1, a peptide released in response to HS, inhibits the actions of insulin on cultured adipocytes through ET-1 type B (ETB) receptors; however, the in vivo implications of ETB receptor activation on lipid metabolism and insulin resistance is unknown. We hypothesized that activation of ETB receptors in response to HS intake promotes dyslipidemia and insulin resistance. In normal salt (NS) fed rats, no significant difference in body mass or epididymal fat mass was observed between control and ETB deficient rats. After 2 weeks of HS, ETB-deficient rats had significantly lower body mass and epididymal fat mass compared to controls. Nonfasting plasma glucose was not different between genotypes; however, plasma insulin concentration was significantly lower in ETB-deficient rats compared to controls, suggesting improved insulin sensitivity. In addition, ETB-deficient rats had higher circulating free fatty acids in both NS and HS groups, with no difference in plasma triglycerides between genotypes. In a separate experiment, ETB-deficient rats had significantly lower fasting blood glucose and improved glucose and insulin tolerance compared to controls. These data suggest that ET-1 promotes adipose deposition and insulin resistance via the ETB receptor.

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16

Terada, Koji, Takahiro Horinouchi, Yoichiro Fujioka, Tsunehito Higashi, Prabha Nepal, Mika Horiguchi, Sarita Karki, et al. "Agonist-promoted Ubiquitination Differentially Regulates Receptor Trafficking of Endothelin Type A and Type B Receptors." Journal of Biological Chemistry 289, no. 51 (November 7, 2014): 35283–95. http://dx.doi.org/10.1074/jbc.m113.544171.

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17

Wei, Feiran, You Ge, Wei Li, Xuerong Wang, and Baoan Chen. "Role of endothelin receptor type B ( EDNRB) in lung adenocarcinoma." Thoracic Cancer 11, no. 7 (May 12, 2020): 1885–90. http://dx.doi.org/10.1111/1759-7714.13474.

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18

Tsaur, Meei-Ling, Yi-Chiou Wan, Fang-Pin Lai, and Hwei-Fang Cheng. "Expression of B-type endothelin receptor gene during neural development." FEBS Letters 417, no. 2 (November 10, 1997): 208–12. http://dx.doi.org/10.1016/s0014-5793(97)01295-7.

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19

Lange, Katrin, Martial Kammerer, Monika E. Hegi, Stefan Grotegut, Antje Dittmann, Wentao Huang, Erika Fluri, et al. "Endothelin Receptor Type B Counteracts Tenascin-C–Induced Endothelin Receptor Type A–Dependent Focal Adhesion and Actin Stress Fiber Disorganization." Cancer Research 67, no. 13 (July 1, 2007): 6163–73. http://dx.doi.org/10.1158/0008-5472.can-06-3348.

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20

Alrashdi, Saeed F., Devy Deliyanti, and Jennifer L. Wilkinson-Berka. "Intravitreal administration of endothelin type A receptor or endothelin type B receptor antagonists attenuates hypertensive and diabetic retinopathy in rats." Experimental Eye Research 176 (November 2018): 1–9. http://dx.doi.org/10.1016/j.exer.2018.06.025.

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21

Mirabito Colafella, Katrina M. "Endothelin type B (ETB) receptors: friend or foe in the pathogenesis of pre-eclampsia and future cardiovascular disease (CVD) risk?" Clinical Science 132, no. 1 (January 2, 2018): 33–36. http://dx.doi.org/10.1042/cs20171366.

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In a recent issue of Clinical Science, Stanhewicz et al. investigated persistent microvascular dysfunction in women up to 16 months postpartum. The authors found sensitivity to the pressor effects of endothelin-1 (ET-1) was enhanced when compared with women who had a normotensive pregnancy. Importantly, the authors demonstrated that this effect was mediated via the endothelin type B (ETB) receptors. Therefore, the present study highlights the possibility that alterations in the localization of the ETB receptor contributes to the pathogenesis of pre-eclampsia and future cardiovascular disease (CVD) risk. Currently, there is great interest in the role of the endothelin system in pre-eclampsia. Targetting the endothelin system, potentially by modulating upstream pathways to prevent ETB receptor dysfunction, may improve health outcomes for women and their offspring during pre-eclampsia and later life.

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Nakaš-Ićindić, Emina, Asija Začiragić, Almira Hadžović, and Nešina Avdagić. "Endothelin in health and disease." Bosnian Journal of Basic Medical Sciences 4, no. 3 (August 20, 2004): 31–34. http://dx.doi.org/10.17305/bjbms.2004.3381.

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Endothelin is a recently discovered peptide composed of 21 amino acids. There are three endothelin isomers: endothelin -1 (ET-1), endothelin -2 (ET-2) and endothelin - 3 (ET-3). In humans and animals levels of ET-1, ET-2, ET-3 and big endothelin in blood range from 0,3 to 3 pg/ml. ET-1, ET-2 and ET-3 act by binding to receptors. Two main types of the receptors for endothelins exist and they are referred to as A and B type receptors. Different factors can stimulate or inhibit production of endothelin by endothelial cells. Mechanical stimulation of endothehum, thrombin, calcium ions, epinephrine, angiotensin II, vasopressin, dopamine, cytokines, growth factors stimulate the production of endothelin whereas nitric oxide, cyclic guanosine monophosphate, atrial natriuretic peptide, prostacyclin, bradykinin inhibit its production. Endothelins have different physiological roles in human body but at the same time their actions are involved in the pathogenesis of many diseases.The aim of this review was to present some of, so far, the best studied physiological roles of endothelin and to summarize evidence supporting the potential role of ET in the pathogenesis of certain diseases.

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LEHRKE, INGO, RÜDIGER WALDHERR, EBERHARD RITZ, and JÜRGEN WAGNER. "Renal Endothelin-1 and Endothelin Receptor Type B Expression in Glomerular Diseases with Proteinuria." Journal of the American Society of Nephrology 12, no. 11 (November 2001): 2321–29. http://dx.doi.org/10.1681/asn.v12112321.

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Abstract. The endothelin (ET) system has been studied extensively in experimental models of progressive chronic renal disease, but there is limited information regarding the ET system in renal patients. First, the expression of human ET-1, as well as ET receptor type A (ET-RA) and ET-RB, was studied in 26 renal biopsies from patients with different renal diseases. Gene expression was assessed by quantitative reverse transcription-PCR. Second, ET-1 and ET-RBprotein expression and localization were examined, by immunohistochemical analyses, among a homogeneous cohort of 16 patients with IgA nephropathy and different degrees of proteinuria. ET-RBmRNA expression was threefold higher among patients with higher-grade proteinuria [≥2 g/24 h,n= 10; OD ratio (ODR),i.e., wild-type/mutant mRNA ratio, 1.81 ± 0.3], compared with patients with lower-grade proteinuria (<2 g/24 h,n= 8; ODR, 0.63 ± 0.1;P< 0.01) or control subjects (n= 9; ODR, 0.57 ± 0.1;P< 0.01). ET-1 gene expression was significantly higher among patients with higher-grade proteinuria, compared with patients with lower-grade proteinuria (P< 0.01) or control subjects (P< 0.05). ET-RAmRNA expression was not different among the groups. Patients with higher-grade proteinuria who were receiving angiotensin-converting enzyme inhibitors exhibited significantly (P< 0.05) lower ET-1 and ET-RBmRNA expression, which was comparable to that of control subjects. By using immunohistochemical analyses, an association between proteinuria and expression of ET-1 and ET-RBin proximal tubular epithelial cells and of ET-1 in glomeruli was confirmed in the separate cohort of patients with IgA nephropathy. It is concluded that the increased ET-RBand ET-1 mRNA and protein expression observed in animal models of renal disease is also demonstrable among patients with renal disease and high-grade proteinuria.

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24

Gonon, Adrian T., Deniz Erbas, Anders Bröijersén, Guro Valen, and John Pernow. "Nitric oxide mediates protective effect of endothelin receptor antagonism during myocardial ischemia and reperfusion." American Journal of Physiology-Heart and Circulatory Physiology 286, no. 5 (May 2004): H1767—H1774. http://dx.doi.org/10.1152/ajpheart.00544.2003.

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Endothelin (ET) receptor antagonism protects from ischemiareperfusion injury. We hypothesized that the cardioprotective effect is related to nitric oxide (NO) bioavailability. Buffer-perfused rat and mouse hearts were subjected to ischemia and reperfusion. At the onset of ischemia, the rat hearts received vehicle, the dual endothelin type A/type B (ETA/ETB) receptor antagonist bosentan (10 μM), the NO synthase inhibitor NG-monomethyl-l-arginine (l-NMMA; 100 μM), the combination of bosentan and l-NMMA or the combination of bosentan, l-NMMA, and the NO substrate l-arginine (1 mM). Hearts from wild-type and endothelial NO synthase (eNOS)-deficient mice received either vehicle or bosentan. Myocardial performance, endothelial function, NO outflow, and eNOS expression were monitored. Bosentan significantly improved myocardial function during reperfusion in rats and in wild-type mice, but not in eNOS-deficient mice. The functional protection afforded by bosentan was inhibited by l-NMMA, whereas it was restored by l-arginine. Myocardial expression of eNOS (immunoblotting) increased significantly in bosentan-treated rat hearts compared with vehicle hearts. Recovery of NO outflow during reperfusion was enhanced in the bosentan-treated rat heart. The endothelium-dependent vasodilator adenosine diphosphate increased coronary flow by 18 ± 9% at the end of reperfusion in the bosentan group, whereas it reduced coronary flow by 7 ± 5% in the vehicle group ( P < 0.001). The response to the endothelium-independent dilator sodium nitroprusside was not different between the two groups. In conclusion, the dual ETA/ETB receptor antagonist bosentan preserved endothelial and cardiac contractile function during ischemia and reperfusion via a mechanism dependent on endothelial NO production.

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Wang, Yongqing, Nezam Altorok, and Bashar Kahaleh. "Potential beneficial role for endothelin in scleroderma vasculopathy: inhibition of endothelial apoptosis by type B endothelin-receptor signaling." Journal of Scleroderma and Related Disorders 1, no. 2 (May 2016): 213–19. http://dx.doi.org/10.5301/jsrd.5000210.

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Matsuura, Kae, Atsushi Sakai, Yuji Watanabe, Yasunori Mikahara, Atsuhiro Sakamoto, and Hidenori Suzuki. "Endothelin receptor type A is involved in the development of oxaliplatin-induced mechanical allodynia and cold allodynia acting through spinal and peripheral mechanisms in rats." Molecular Pain 17 (January 2021): 174480692110580. http://dx.doi.org/10.1177/17448069211058004.

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Oxaliplatin, a platinum-based chemotherapeutic agent, frequently causes severe neuropathic pain typically encompassing cold allodynia and long-lasting mechanical allodynia. Endothelin has been shown to modulate nociceptive transmission in a variety of pain disorders. However, the action of endothelin varies greatly depending on many variables, including pain causes, receptor types (endothelin type A (ETA) and B (ETB) receptors) and organs (periphery and spinal cord). Therefore, in this study, we investigated the role of endothelin in a Sprague–Dawley rat model of oxaliplatin-induced neuropathic pain. Intraperitoneal administration of bosentan, a dual ETA/ETB receptor antagonist, effectively blocked the development or prevented the onset of both cold allodynia and mechanical allodynia. The preventive effects were exclusively mediated by ETA receptor antagonism. Intrathecal administration of an ETA receptor antagonist prevented development of long-lasting mechanical allodynia but not cold allodynia. In marked contrast, an intraplantar ETA receptor antagonist had a suppressive effect on cold allodynia but only had a partial and transient effect on mechanical allodynia. In conclusion, ETA receptor antagonism effectively prevented long-lasting mechanical allodynia through spinal and peripheral actions, while cold allodynia was prevented through peripheral actions.

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ETOH, NOBUAKI, MOTOHIRO KONDOH, JUNJI OHNISHI, KAZUO MURAKAMI, and HITOSHI MIYAZAKI. "CHARACTERIZATION OF RECOMBINANT ENDOTHELIN RECEPTOR TYPE B OVEREXPRESSED IN CHINESE HAMSTER OVARY CELLS ." Biomedical Research 15, no. 5 (1994): 299–309. http://dx.doi.org/10.2220/biomedres.15.299.

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Romanelli, Roberto G., Tullio Barni, Mario Maggi, Michaela Luconi, Paola Failli, Anna Pezzatini, Annamaria Morelli, et al. "Role of Endothelin-1 in the Migration of Human Olfactory Gonadotropin-Releasing Hormone-Secreting Neuroblasts." Endocrinology 146, no. 10 (October 1, 2005): 4321–30. http://dx.doi.org/10.1210/en.2005-0060.

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FNC-B4 neuroblasts that express both neuronal and olfactory markers have been established and cloned. These cells express GnRH and both the endothelin-1 (ET-1) gene and protein and respond in a migratory manner to GnRH in a dose-dependent manner. Previous research has shown that FNC-B4 cells produce and respond to ET-1 by regulating the secretion of GnRH through endothelin type A receptors and by stimulating their proliferation through endothelin type B (ETB) receptors. In this study, we found that FNC-B4 cells are able to migrate in response to ET-1 through the involvement of ETB receptors. Combined immunohistochemical and biochemical analyses showed that ET-1 triggered actin cytoskeletal remodeling and a dose-dependent increase in migration (up to 6-fold). Whereas the ETB receptor antagonist (B-BQ788) blunted the ET-1-induced effects, the ETA receptor antagonist (A-BQ123) did not. Moreover, we observed that FNC-B4 cells were independently and selectively stimulated by ET-1 and GnRH. We suggest that ET-1, through ETB receptor activation, may be required to maintain an adequate proliferative stem cell pool in the developing olfactory epithelium and the subsequent commitment to GnRH neuronal migratory pattern. The coordinate interaction between ET receptors and GnRH receptor participates in the fully expressed GnRH-secreting neuron phenotype.

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Evans, JJ, AH Youssef, TG Yandle, LK Lewis, and MG Nicholls. "Effects of endothelin-1 on release of adrenomedullin and C-type natriuretic peptide from individual human vascular endothelial cells." Journal of Endocrinology 175, no. 1 (October 1, 2002): 225–32. http://dx.doi.org/10.1677/joe.0.1750225.

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Regulation of cardiovascular system activity involves complex interactions amongst numerous factors. Three of these vasoactive factors are adrenomedullin, C-type natriuretic peptide (CNP) and endothelin-1 (ET-1), each of which is claimed to have important local effects. To investigate paracrine/autocrine regulation of the secretion of these peptides we used a cell immunoblot method. We postulated that basal release of adrenomedullin and CNP by endothelial cells is modulated by ET-1. Dispersed human aortic endothelial cells were attached to a protein binding membrane and incubated for 1 or 4 h with control medium or with ET-1, endothelin receptor antagonists or antibody to ET-1, and then submitted to immunohistochemical staining. Peptides (adrenomedullin, CNP and ET-1) within individual cells were stained, as was peptide secreted and adjacent to the cell. It was demonstrated that adrenomedullin, CNP and ET-1 can be contained within the same cell. In addition, we observed that individual endothelial cells can secrete all three peptides. The endothelin ET-A/ET-B receptor antagonist, bosentan, the ET-B receptor antagonist, BQ-788, and anti-ET-1 serum decreased the percentage of endothelial cells that secreted adrenomedullin and CNP relative to control. Conversely, the addition of ET-1 induced an increase in the number of endothelial cells that secreted adrenomedullin and CNP. These results provide strong evidence that endogenous ET-1, from human vascular endothelial cells, acts in a paracrine/autocrine manner to modulate the basal release of adrenomedullin and CNP. Our observations of this modulation suggest that vascular endothelial cells of humans constitute an important component of a self-responsive vasoregulatory system.

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Tsuboi, Ryoji, Chiyo Sato, and Hideoki Ogawa. "UVB irradiation increases endothelin-1 and type B endothelin receptor expressions in cultured human keratinocytes." Journal of Dermatological Science 6, no. 1 (August 1993): 41. http://dx.doi.org/10.1016/0923-1811(93)90957-q.

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31

Bkaily, Ghassan, Levon Avedanian, Johny Al-Khoury, Chantale Provost, Moni Nader, Pedro D'Orléans-Juste, and Danielle Jacques. "Nuclear membrane receptors for ET-1 in cardiovascular function." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 300, no. 2 (February 2011): R251—R263. http://dx.doi.org/10.1152/ajpregu.00736.2009.

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Plasma membrane endothelin type A (ETA) receptors are internalized and recycled to the plasma membrane, whereas endothelin type B (ETB) receptors undergo degradation and subsequent nuclear translocation. Recent studies show that G protein-coupled receptors (GPCRs) and ion transporters are also present and functional at the nuclear membranes of many cell types. Similarly to other GPCRs, ETA and ETB are present at both the plasma and nuclear membranes of several cardiovascular cell types, including human cardiac, vascular smooth muscle, endocardial endothelial, and vascular endothelial cells. The distribution and density of ETARs in the cytosol (including the cell membrane) and the nucleus (including the nuclear membranes) differ between these cell types. However, the localization and density of ET-1 and ETB receptors are similar in these cell types. The extracellular ET-1-induced increase in cytosolic ([Ca]c) and nuclear ([Ca]n) free Ca2+ is associated with an increase of cytosolic and nuclear reactive oxygen species. The extracellular ET-1-induced increase of [Ca]c and [Ca]n as well as intracellular ET-1-induced increase of [Ca]n are cell-type dependent. The type of ET-1 receptor mediating the extracellular ET-1-induced increase of [Ca]c and [Ca]n depends on the cell type. However, the cytosolic ET-1-induced increase of [Ca]n does not depend on cell type. In conclusion, nuclear membranes' ET-1 receptors may play an important role in overall ET-1 action. These nuclear membrane ET-1 receptors could be targets for a new generation of antagonists.

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Li, Xiao Xi, Martin Bek, Laureano D. Asico, Zhiwei Yang, David K. Grandy, David S. Goldstein, Marcelo Rubinstein, Gilbert M. Eisner, and Pedro A. Jose. "Adrenergic and Endothelin B Receptor-Dependent Hypertension in Dopamine Receptor Type-2 Knockout Mice." Hypertension 38, no. 3 (September 2001): 303–8. http://dx.doi.org/10.1161/01.hyp.38.3.303.

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Seif, Faezeh, Peter J. Little, Reyhaneh Niayesh‐Mehr, Masoumeh Zamanpour, and Hossein Babaahmadi‐Rezaei. "Endothelin‐1 increases CHSY ‐1 expression in aortic endothelial cells via transactivation of transforming growth factor β type I receptor induced by type B receptor endothelin‐1." Journal of Pharmacy and Pharmacology 71, no. 6 (February 27, 2019): 988–95. http://dx.doi.org/10.1111/jphp.13081.

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Deliu, Elena, G. Cristina Brailoiu, Karthik Mallilankaraman, Hong Wang, Muniswamy Madesh, Ashiwel S. Undieh, Walter J. Koch, and Eugen Brailoiu. "Intracellular Endothelin Type B Receptor-driven Ca2+Signal Elicits Nitric Oxide Production in Endothelial Cells." Journal of Biological Chemistry 287, no. 49 (October 19, 2012): 41023–31. http://dx.doi.org/10.1074/jbc.m112.418533.

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Eguchi, S., Y. Hirata, T. Imai, and F. Marumo. "C-type natriuretic peptide upregulates vascular endothelin type B receptors." Hypertension 23, no. 6_pt_2 (June 1994): 936–40. http://dx.doi.org/10.1161/01.hyp.23.6.936.

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Yoshimura, Ashio, Shigeki Iwasaki, Kiyoko Inui, Terukuni Ideura, Shozo Koshikawa, Masashi Yanagisawa, and Tomoh Masaki. "Endothelin-1 and endothelin B type receptor are induced in mesangial proliferative nephritis in the rat." Kidney International 48, no. 4 (October 1995): 1290–97. http://dx.doi.org/10.1038/ki.1995.413.

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Bender, S. B., and R. E. Klabunde. "Altered role of smooth muscle endothelin receptors in coronary endothelin-1 and α1-adrenoceptor-mediated vasoconstriction in Type 2 diabetes." American Journal of Physiology-Heart and Circulatory Physiology 293, no. 4 (October 2007): H2281—H2288. http://dx.doi.org/10.1152/ajpheart.00566.2007.

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Regulation of vascular tone and blood flow involves interactions between numerous local and systemic vascular control signals, many of which are altered by Type 2 diabetes (T2D). Vascular responses to endothelin-1 (ET-1) are mediated by endothelin type A (ETA) and type B (ETB) receptors that have been implicated in cross talk with α1-adrenoceptors (α1-AR). ETA and ETB receptor expression and plasma ET-1 levels are elevated in T2D; however, whether this influences coronary α1-AR function has not been examined. Therefore, we examined the effect of ETA and ETB receptor inhibition on coronary vasoconstriction to ET-1 and α1-AR activation in a mouse model of T2D. Coronary vascular responses were examined in isolated mouse hearts from control and diet-induced T2D C57BL/6J mice. Responses to ET-1 and the selective α1-AR agonist phenylephrine (PE) were examined alone and in the presence of the nitric oxide synthase inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) alone or in combination with selective ETA or ETB receptor inhibitors BQ-123 and BQ-788, respectively. Vasoconstriction to ET-1 was enhanced, whereas ETB, but not ETA, receptor blockade reduced basal coronary tone in T2D hearts. In the presence of l-NAME, ETA receptor inhibition attenuated ET-1 vasoconstriction in both groups, whereas ETB inhibition abolished this response only in control hearts. In addition, ETA inhibition enhanced α1-AR-mediated vasoconstriction in T2D, but not control, hearts following l-NAME treatment. Therefore, in this model, enhanced coronary ET-1 responsiveness is mediated primarily through smooth muscle ETB receptors, whereas the interaction with α1-ARs is mediated solely through the ETA receptor subtype.

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Clozel, M., B. M. Loffler, V. Breu, L. Hilfiger, J. P. Maire, and B. Butscha. "Downregulation of endothelin receptors by autocrine production of endothelin-1." American Journal of Physiology-Cell Physiology 265, no. 1 (July 1, 1993): C188—C192. http://dx.doi.org/10.1152/ajpcell.1993.265.1.c188.

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The potent vasoconstrictor endothelin-1 (ET-1) is a paracrine, but also autocrine, factor for some types of cells. The goal of our study was to evaluate whether the receptor population in cells expressing endothelin receptor subtype A (rat mesangial cells) or endothelin receptor subtype B (human and rat endothelial cells) was affected by the autocrine production of ET-1. We therefore studied maximal binding capacity of 125I-labeled ET-1 in the presence or absence of the metalloprotease inhibitors phosphoramidon, which blocks the intracellular processing of Big ET-1 to ET-1, and thiorphan, which does not block this conversion. Phosphoramidon inhibited the release of ET-1 by human umbilical vein endothelial cells, rat aortic endothelial cells, and rat mesangial cells, and increased 1.4- to 17-fold the maximal binding capacity in the three types of cells. Thiorphan affected neither ET-1 release nor binding. The increase in receptor binding by phosphoramidon was associated with an increase in the functional effect of ET-1, as measured by arachidonic acid release in rat mesangial cells. We conclude that autocrine production of ET-1 decreases, either by binding or by downregulation, the number of binding sites available for ET-1 of paracrine or systemic sources. This aspect of modulation of the vasoconstrictor effect of endothelin should be considered in pathological situations or after endothelin-converting-enzyme inhibition.

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Chen, Gin-Fu, and Zhongjie Sun. "Effects of chronic cold exposure on the endothelin system." Journal of Applied Physiology 100, no. 5 (May 2006): 1719–26. http://dx.doi.org/10.1152/japplphysiol.01407.2005.

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Cold temperatures have adverse effects on the human cardiovascular system. Endothelin (ET)-1 is a potent vasoconstrictor. We hypothesized that cold exposure increases ET-1 production and upregulates ET type A (ETA) receptors. The aim of this study was to determine the effect of cold exposure on regulation of the ET system. Four groups of rats (6–7 rats/group) were used: three groups were exposed to moderate cold (6.7 ± 2°C) for 1, 3, and 5 wk, respectively, and the remaining group was maintained at room temperature (25°C) and served as control. Cold exposure significantly increased ET-1 levels in the heart, mesenteric arteries, renal cortex, and renal medulla. Cold exposure increased ETA receptor protein expression in the heart and renal cortex. ET type B (ETB) receptor expression, however, was decreased significantly in the heart and renal medulla of cold-exposed rats. Cold exposure significantly increased the ratio of ETA to ETB receptors in the heart. An additional four groups of rats (3 rats/group) were used to localize changes in ETA and ETB receptors at 1, 3, and 5 wk of cold exposure. Immunohistochemical analysis showed an increase in ETA, but a decrease in ETB, receptor immunoreactivity in cardiomyocytes of cold-exposed rats. Increased ETA receptor immunoreactivity was also found in vascular smooth muscle cells of cold-exposed rats. Cold exposure increased ETA receptor immunoreactivity in tubule epithelial cells in the renal cortex but decreased ETB receptor immunoreactivity in tubule epithelial cells in the renal medulla. Therefore, cold exposure increased ET-1 production, upregulated ETA receptors, and downregulated ETB receptors.

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Higo, Junichi, Kota Kasahara, Mitsuhito Wada, Bhaskar Dasgupta, Narutoshi Kamiya, Tomonori Hayami, Ikuo Fukuda, Yoshifumi Fukunishi, and Haruki Nakamura. "Free-energy landscape of molecular interactions between endothelin 1 and human endothelin type B receptor: fly-casting mechanism." Protein Engineering, Design and Selection 32, no. 7 (July 2019): 297–308. http://dx.doi.org/10.1093/protein/gzz029.

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Abstract The free-energy landscape of interaction between a medium-sized peptide, endothelin 1 (ET1), and its receptor, human endothelin type B receptor (hETB), was computed using multidimensional virtual-system coupled molecular dynamics, which controls the system’s motions by introducing multiple reaction coordinates. The hETB embedded in lipid bilayer was immersed in explicit solvent. All molecules were expressed as all-atom models. The resultant free-energy landscape had five ranges with decreasing ET1–hETB distance: completely dissociative, outside-gate, gate, binding pocket, and genuine-bound ranges. In the completely dissociative range, no ET1–hETB interaction appeared. In the outside-gate range, an ET1–hETB attractive interaction was the fly-casting mechanism. In the gate range, the ET1 orientational variety decreased rapidly. In the binding pocket range, ET1 was in a narrow pathway with a steep free-energy slope. In the genuine-bound range, ET1 was in a stable free-energy basin. A G-protein-coupled receptor (GPCR) might capture its ligand from a distant place.

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Honoré, Jean-Claude, Marie-Hélène Fecteau, Isabelle Brochu, Julie Labonté, Ghassan Bkaily, and Pedro D’Orleans-Juste. "Concomitant antagonism of endothelial and vascular smooth muscle cell ETB receptors for endothelin induces hypertension in the hamster." American Journal of Physiology-Heart and Circulatory Physiology 289, no. 3 (September 2005): H1258—H1264. http://dx.doi.org/10.1152/ajpheart.00352.2005.

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In the vascular system, endothelin (ET) type B (ETB) receptors for ET-1 are located on endothelial and on venous and arterial smooth muscle cells. In the present study, we investigated the hemodynamic effects of chronic ETB receptor blockade at low and high doses in the Syrian Golden hamster. After 16 days of gavage with A-192621 (0.5 or 30 mg·kg−1·day−1), a selective ETB receptor antagonist, hamsters were anesthetized with a mixture of ketamine and xylazine (87 and 13 mg/kg im, respectively), and basal mean arterial blood pressure (MAP) and pressor responses to exogenous ET-1 were evaluated. The lower dose of A-192621 (0.5 mg·kg−1·day−1) did not modify basal MAP, whereas the higher dose (30 mg·kg−1·day−1) increased MAP and plasma ET levels. Radio-telemetry recordings confirmed the increase in MAP induced by the higher dose of A-192621 in conscious hamsters. On the other hand, although the lower dose of A-192621 was devoid of intrinsic pressor effects, it markedly reduced the transient hypotensive phase induced by intravenously injected IRL-1620, a selective ETB receptor agonist. Finally, A-192621 (0.5 mg·kg−1·day−1) alone or A-192621 (30 mg·kg−1·day−1) + atrasentan (6 mg·kg−1·day−1), a selective ETA receptor antagonist, potentiated the pressor response to exogenous ET-1. Our results suggest that, in the hamster, ETB receptors on vascular smooth muscle cells are importantly involved in the clearance of endogenous ET-1, whereas the same receptor type on the endothelium is solely involved in the vasodilatory responses to the pressor peptide. Blockade of endothelial and vascular smooth muscle cell ETB receptors triggers a marked potentiation of ETA-dependent increases in systemic resistance.

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Ayala-Valdovinos, Miguel Angel, Jorge Galindo-García, David Sánchez-Chiprés, and Theodor Duifhuis-Rivera. "New test for endothelin receptor type B (EDNRB) mutation genotyping in horses." Molecular and Cellular Probes 30, no. 3 (June 2016): 182–84. http://dx.doi.org/10.1016/j.mcp.2016.03.005.

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Xu, Cang-Bao, Jian-Pu Zheng, Wei Zhang, Enqi Liu, Lars Edvinsson, and Yaping Zhang. "Low density lipoprotein induces upregulation of vasoconstrictive endothelin type B receptor expression." Vascular Pharmacology 60, no. 1 (January 2014): 42–48. http://dx.doi.org/10.1016/j.vph.2013.11.004.

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44

Mazzuca, Marc Q., and Raouf A. Khalil. "Vascular endothelin receptor type B: Structure, function and dysregulation in vascular disease." Biochemical Pharmacology 84, no. 2 (July 2012): 147–62. http://dx.doi.org/10.1016/j.bcp.2012.03.020.

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Schläpfer, Jörg, Daniel S. Gallagher, Jay D. Burzlaff, Scott K. Davis, Jeremy F. Taylor, and James E. Womack. "Physical mapping of the endothelin receptor type B to bovine chromosome 12." Mammalian Genome 8, no. 5 (May 1997): 380–81. http://dx.doi.org/10.1007/s003359900447.

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46

Zeng, Zhizhen, Kui Su, Hla Kyaw, and Yi Li. "A Novel Endothelin Receptor Type-B-like Gene Enriched in the Brain." Biochemical and Biophysical Research Communications 233, no. 2 (April 1997): 559–67. http://dx.doi.org/10.1006/bbrc.1997.6408.

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Zhang, Min-Yu, Fei-Fei Guo, Hong-Wei Wu, Yang-Yang Yu, Jun-Ying Wei, Shi-Feng Wang, Yu-Xin Zhang, et al. "DanHong injection targets endothelin receptor type B and angiotensin II receptor type 1 in protection against cardiac hypertrophy." Oncotarget 8, no. 61 (October 13, 2017): 103393–409. http://dx.doi.org/10.18632/oncotarget.21900.

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48

Kapur, R. P., D. A. Sweetser, B. Doggett, J. R. Siebert, and R. D. Palmiter. "Intercellular signals downstream of endothelin receptor-B mediate colonization of the large intestine by enteric neuroblasts." Development 121, no. 11 (November 1, 1995): 3787–95. http://dx.doi.org/10.1242/dev.121.11.3787.

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Mice homozygous for the piebald lethal (sl) mutation, which have a complete deletion of endothelin receptor-B, fail to form ganglion cells in the distal large intestine and are nearly devoid of cutaneous melanocytes. These phenotypic features stem from incomplete colonization of the hindgut and skin by neural crest-derived neuroblasts and melanoblasts, respectively. We have used expression of a transgene, dopamine-beta-hydroxylase-nlacZ, to study colonization of the enteric nervous system in sl/sl embryos and sl/sl <--> wild-type chimeric mice. Enteric neuroblasts derived from the vagal neural crest colonize the developing foregut, midgut and distal small intestine of sl/sl embryos in a cranial-to-caudal manner indistinguishable from sl/+ or +/+ embryos. However, colonization of the large intestine is retarded and the distal large intestine is never colonized, a developmental defect identical to that observed in lethal spotted (endothelin-3 deficient) embryos. The coat pigmentation and relative distributions of mutant and wild-type ganglion cells in sl/sl <--> wild-type chimeras indicate that the defect associated with endothelin receptor-B gene deletion is not strictly neuroblast autonomous (independent of environmental factors). Instead, intercellular interactions downstream of the endothelin receptor-B mediate complete colonization of the skin and gut by neural crest cells.

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Cervar-Zivkovic, M., M. Dieber-Rotheneder, S. Barth, T. Hahn, G. Kohnen, B. Huppertz, U. Lang, and G. Desoye. "Endothelin-1 Stimulates Proliferation of First-Trimester Trophoblasts via the A- and B-Type Receptor and Invasion via the B-Type Receptor." Journal of Clinical Endocrinology & Metabolism 96, no. 11 (November 1, 2011): 3408–15. http://dx.doi.org/10.1210/jc.2011-0634.

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Abstract Context: Endothelin-1 (ET-1) stimulates proliferation and invasion of first-trimester human trophoblast cells. Objective: To test the hypothesis that ET-1 effects are mediated by different receptor subtypes [ET receptor (ETR)-A and ETR-B]. Design: The location of ETR in trophoblast cell columns (wk 6–12) was investigated by immunohistochemistry and autoradiography. Trophoblasts were isolated from first-trimester human placentas and proliferative and invasive subpopulations separated using an integrin α6 antibody. Cells were incubated for 24 h with 10 μm ET-1 and different ETR antagonists: PD142893 (unselective), BQ-610 (ETR-A), and RES-701-1 (ETR-B). After ETR down-regulation by antisense oligonucleotides, proliferation (thymidine incorporation, protein synthesis) and invasion (Matrigel invasion) were measured. ETR expression in isolated cells was analyzed by Western blotting and semiquantitative RT-PCR. Results: Both ETR are expressed in both subpopulations in the cell column with predominance of ETR-A in the proximal part and proliferative subpopulation, whereas ETR-B is present at similar levels in both subpopulations. These results were confirmed at the mRNA level. ET-1 increased proliferation (maximum 267% of control) and invasion (maximum 288% of control) of first-trimester trophoblasts. The mitogenic ET-1 effect was inhibited (P < 0.05) by 40–80% with each receptor antagonist and by 44 and 40%, respectively, by ETR-A and ETR-B antisense oligonucleotides. The invasion-promoting effect was almost completely blocked in the presence of the ETR-B antagonists. Conclusion: The effect of ET-1 on cell proliferation in first-trimester trophoblasts is mediated by both ETR, whereas its effect on invasion is mediated predominantly by ETR-B. These effects are in line with the receptor subtype location.

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Hegner, B., R. Schindler, G. Riemekasten, P. Scheerer, A. Philippe, and R. Catar. "POS0474 ACTIVATION AND HYPERSENSITIZATION OF THE ANGIOTENSIN II TYPE 1 AND ENDOTHELIN-1 TYPE A RECEPTORS BY AGONISTIC AUTOANTIBODIES CONTRIBUTES TO VASCULAR INJURY IN SCLERODERMA RENAL CRISIS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 491.2–492. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1649.

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BackgroundScleroderma renal crisis (SRC) is a vascular complication of systemic sclerosis (SSc) with substantial risks for end-stage renal disease and death. Activating autoantibodies (Abs) targeting the angiotensin II type 1 (AT1R) and the endothelin-1 type A receptor (ETAR) are suggested to contribute to the vasculopathy in SSc (1, 2).ObjectivesHere, we sought to determine their pathogenic significance for acute renal vascular injury.MethodsIgG from patients with SRC was studied for AT1R and ETAR dependent biologic effects on isolated rat renal interlobar arteries and vascular cells including contraction, signaling, and mechanisms of receptor activation. A cohort of ten patients with refractory SRC received multimodal treatment including AT1R and ETAR inhibition and plasma exchange and was followed for improvement of kidney function.ResultsIn myography experiments, patient IgG exerted vasoconstriction (mean 6.5% of KCl induced contraction [95% confidence interval (95 CI) 5.0-8.1]) whereas control IgG did not (0.6% [95 CI 0.3-1.0]). The response was sensitive to inhibition of AT1R (3.0% [95% CI 1.4-4.7]) and ETAR (1.0% [95 CI 0.6-1.3]) and relied on MEK-ERK signaling. Contraction induced by angiotensin II and endothelin-1 was amplified by anti-AT1R and anti-ETAR Abs with substantial crosstalk between both receptors implicating autoimmune receptor hypersensitization. Co-immunoprecipitation experiments indicated heterodimerization between both receptor types enabling functional interrelation by structural interactions. 30% of patients with refractory SRC had improved kidney function after multimodal therapy.ConclusionWe provide experimental and clinical evidence that agonistic Abs may contribute to SRC. Novel therapies targeted at autoimmune hyperactivation of AT1R and ETAR might improve outcomes in severe cases of SRC.References[1]Riemekasten, G. et al. Involvement of functional autoantibodies against vascular receptors in systemic sclerosis. Ann. Rheum. Dis. 70, 530–536 (2011).[2]Becker, M. O. et al. Vascular receptor autoantibodies in pulmonary arterial hypertension associated with systemic sclerosis. Am. J. Respir. Crit. Care Med. 190, 808–817 (2014).Figure 1.Contraction of isolated rat renal interlobar arteries in response to IgG isolated from patients with scleroderma renal crisis (SRC) is dependent on angiotensin II typ 1 (AT1R) and endothelin-1 type A receptors (ETAR). Small vessel myography of artery rings exposed to (a) different concentrations of IgG isolated from healthy controls (Control IgG) or patients with SRC (SRC IgG). n = 12. *P<0.001 for SRC IgG versus Control IgG, #P<0.01 for 1.0 mg/mL versus 0.25 mg/mL and P<0.05 for 1.0 mg/mL versus 0.5 mg/mL. (b) Myography of vessels exposed to 1.0 mg/mL Control IgG or SRC IgG after pretreatment with an AT1R blocker (AT1RB, valsartan), an ETAR blocker (ETARB, sitaxsentan) or a dual endothelin-1 type A and type B receptor blocker (ETA/BRB, bosentan). n = 12. **P<0.01, ***P<0.001. Contraction is expressed as % of the maximal contraction in response to 60 mM KCl of each individual vessel. Mean±SEM.Figure 2.Interdependence of the angiotensin II (AngII) type 1 receptor (AT1R) and endothelin-1 (ET-1) receptors (ETA/BR) in the contractile response of isolated rat renal interlobar arteries to AngII and ET-1 in the presence of anti- AT1R and anti-ETAR activating autoantibodies.Small vessel myography of artery rings exposed to 1.0 mg/mL IgG isolated from healthy controls (Control IgG) or patients with scleroderma renal crisis (SRC IgG) and natural ligands with and without pretreatment with receptor blockers as indicated. (a) Additional stimulation with 1000 nM AngII ± ETA/BR blocker (ETA/BRB) bosentan. n = 11-18. (b) Additional stimulation with 100 nM ET-1 ± AT1R blocker (AT1RB) valsartan. n = 6-12. Contraction is expressed as % of the maximal contraction in response to 60 mM KCl of each individual vessel. Mean±SEM. **P<0.01, ***P<0.001.Disclosure of InterestsNone declared.

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Journal articles on the topic 'Endothelin receptor – type B'

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