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Endothelin Receptor-Effector Coupling and Signaling in Cardiac Cells
Published in Malcolm J. Lewis, Ajay M. Shah, Endothelial Modulation of Cardiac Function, 2020
In experiments involving assessment of ligand binding or physiologic or biochemical responses to ET, the receptor types can be distinguished pharmacologically by their affinities for ET isoforms and for sarafotoxins (S6), structurally homologous snake toxins (Douglas et al., 1994; Bax and Saxena, 1994). The ETA receptor is selective for ET-1 ≥ ET-2 ≫ ET-3, with sarafotoxin 6c being inactive. The ETB receptor is nonselective: ET-1 = ET-2 = ET-3 = S6c. The recently described ETC receptor prefers ET-3 and exhibits lower apparent affinities for the other compounds.
Endothelium
Published in Neil Herring, David J. Paterson, Levick's Introduction to Cardiovascular Physiology, 2018
Neil Herring, David J. Paterson
Endothelins are a family of peptides related to the snake venom sarafotoxin. Endothelin 1 (ET-1), the main isoform secreted by the endothelium, causes a powerful, unusually sustained vasoconstriction, lasting 2-3 h. ET-1 activates myocyte ETA receptors, which are coupled via a G protein to the myocyte PLC/IP3 system. The resulting rise in myocyte Ca2+ triggers vasoconstriction. Over a longer timescale, ET also stimulates vascular and cardiac myocyte proliferation.
Production of Contracting Agents
Published in Thomas F. Lüscher, Paul M. Vanhoutte, The Endothelium: Modulator of Cardiovascular Function, 2020
Thomas F. Lüscher, Paul M. Vanhoutte
Ca2+ — The structural similarity with neurotoxins (apamin, α-scorpion toxin, sarafotoxin) originally suggested that endothelin may act directly on ion channels, in particular the voltage-operated Ca2+ channels.19,20,646,67,699,1223,1419 However, the contractions induced by endothelin differ from those obtained with the Ca2+-channel agonist Bay K 8644.45,1371 The peptide binds to specific receptors on the cell membrane of vascular smooth muscle (see References 182, 224, 227,453,499, 500, 526,670, 856,913,935, and 980) or possibly to several receptor subtypes which may be differently activated by the three isomers of the peptide.1187 This binding is not affected by Ca2+ antagonists.156,182 In certain blood vessels, Ca2+ antagonists do not affect the contractions induced by endothelin (Figure 16). Thus, endothelin cannot be considered as a natural agonist at voltage-dependent Ca2+ channels. However, in certain vascular smooth muscle, such as the porcine coronary artery, the peptide can activate voltage-operated Ca2+ channels and in turn evoke the influx of extracellular Ca2+.419 This would explain why Ca2+antagonists can attenuate (but not prevent) endothelin-induced contractions in some vascular smooth muscle.156,268,558,1189,1324,1371,1419,1427 Activation of sodium channels also is not essential for the vascular action of endothelin.101
Synergistic effects of a cremophor EL drug delivery system and its U0126 cargo in an ex vivo model
Published in Drug Delivery, 2019
S. T. Christensen, A. S. Grell, S. E. Johansson, C. M. Andersson, L. Edvinsson, K. A. Haanes
Subsequently, concentration-response curves were obtained by the cumulative application of the specific ligand for the ETB receptor, Sarafotoxin 6c (S6c, Polypeptide, Sweden), in the concentration range of 10−14 to 10−7 M (Henriksson et al., 2004).