Endothelin 1 (swine, human) is a 21aa peptide vasoconstrictor and agonist of endothelin (ET) receptors ETA and ETB (IC50s = 0.15 and 0.12 nM, respectively) [1]. Endothelin 1 (swine, human) is the endothelin generated in the endothelium, where it acts in a paracrine or autocrine manner on ETA and ETB receptors on adjacent endothelial or smooth muscle cells [2].
Endothelin 1 (swine, human) activats endothelin-A receptor (ETAR) and drives epithelial-to-mesenchymal transition in ovarian tumor cells through b-arrestin signaling. In cultured mouse podocytes, Endothelin 1 (swine, human) caused loss of the podocyte differentiation marker synaptopodin and acquisition of the mesenchymal marker a-smooth muscle actin. Endothelin 1 (swine, human) promoted podocyte migration via ETAR activation and increased b-arrestin-1 expression [3].
The Endothelin 1 (swine, human) (1nmol/kg) produced strong pressor responses in the anesthetized rats in vivo [4]. Mice received an intradermal injection of 1-30 pmol Endothelin 1 (swine, human) and were caused dose-dependent scratching bouts [5]. A subpressor dose of ET-1 administered to rats was found to increase glomerular permeability and inflammation as well as the excretion of the glomerular slit-diaphragm protein nephrin, effects that could be blocked by an ETA receptor antagonist [6]. The magnitude of the ET-1 rise during antiangiogenic treatment may be useful biomarker of the efficacy of treatment [7].
References:
[1]. Kikuchi T, Kubo K, Ohtaki T, et al. Endothelin-1 analogues substituted at both position 18 and 19: highly potent endothelin antagonists with no selectivity for either receptor subtype ETA or ETB[J]. Journal of medicinal chemistry, 1993, 36(25): 4087-4093.
[2]. Schiffrin E L. Role of endothelin-1 in hypertension and vascular disease[J]. American journal of hypertension, 2001, 14(S3): 83S-89S.
[3]. Buelli S, Rosanò L, Gagliardini E, et al. β-Arrestin-1 drives endothelin-1-mediated podocyte activation and sustains renal injury[J]. Journal of the American Society of Nephrology, 2014, 25(3): 523-533.
[4]. Inoue A, Yanagisawa M, Kimura S, et al. The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes[J]. Proceedings of the national academy of sciences, 1989, 86(8): 2863-2867.
[5]. Trentin P G, Fernandes M B, D'Orléans-Juste P, et al. Endothelin-1 causes pruritus in mice[J]. Experimental biology and medicine, 2006, 231(6): 1146-1151.
[6]. Saleh M A, Pollock J S, Pollock D M. Distinct actions of endothelin A-selective versus combined endothelin A/B receptor antagonists in early diabetic kidney disease[J]. Journal of Pharmacology and Experimental Therapeutics, 2011, 338(1): 263-270.
[7]. Lankhorst S, Jan Danser A H, van den Meiracker A H. Endothelin-1 and antiangiogenesis[J]. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2016, 310(3): R230-R234.
内皮素 1（猪、人）是一种 21aa 肽血管收缩剂和内皮素 (ET) 受体 ETA 和 ETB 的激动剂（IC50 分别 = 0.15 和 0.12 nM）[1]。内皮素 1（猪、人）是在内皮细胞中产生的内皮素,它以旁分泌或自分泌的方式作用于相邻内皮细胞或平滑肌细胞上的 ETA 和 ETB 受体[2]。
内皮素 1（猪、人）激活内皮素 A 受体 (ETAR) 并通过 b-arrestin 信号传导驱动卵巢肿瘤细胞的上皮-间质转化。在培养的小鼠足细胞中,内皮素 1（猪、人）导致足细胞分化标志物突触蛋白的丢失和间充质标志物 a-平滑肌肌动蛋白的获得。内皮素 1（猪、人）通过 ETAR 激活促进足细胞迁移并增加 b-arrestin-1 表达[3]。
内皮素 1（猪、人）(1nmol/kg) 在麻醉大鼠体内产生强烈的升压反应 [4]。小鼠皮内注射 1-30 pmol 内皮素 1（猪、人）并引起剂量依赖性抓挠发作 [5]。研究发现,给大鼠施用降压剂量的 ET-1 可增加肾小球通透性和炎症以及肾小球裂隙隔膜蛋白肾素的排泄,这些作用可被 ETA 受体拮抗剂阻断[6]。抗血管生成治疗期间 ET-1 升高的幅度可能是治疗疗效的有用生物标志物[7]。