Abstract
By painstakingly seeking and purifying a novel vasoconstrictor from the supernatants of large-scale cultures of endothelial cells, the 21 amino acid peptide endothelin-1 (ET-1) was discovered by Yanagisawa and co-workers1 in Japan in 1988. They showed that it was synthesized in two stages by cleavage of a large precursor (prepro-ET-1), was structurally related to a snake venom toxin, and was a highly potent long-lasting vasoconstrictor (acting in the nanomolar range; still one of the most potent vasoconstrictors known). Within a few years, it had been shown that ET-1 secretion from endothelial cells can be enhanced by a series of cytokines, hypoxia, mechanical stress, and other stimuli, and that its action is mediated by two G-protein coupled receptors, ET(A) and ET(B).2 These receptors are almost 50% identical with similar affinity for ET-1. Both are linked to elevation of intracellular calcium ions, and activation of several kinase signaling pathways, which are likely to differ in different cell types.
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Acknowledgments
Research from the authors’ labs summarized here was funded by The Arthritis Research Campaign, The Wellcome Trust, and Raynaud’s & Scleroderma Association.
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Pearson, J.D., Shi-wen, X., Howat, S.L., Denton, C.P., Abraham, D.J. (2009). Endothelin-1 and Systemic Sclerosis. In: Abraham, D., Clive, H., Dashwood, M., Coghlan, G. (eds) Advances in Vascular Medicine. Springer, London. https://doi.org/10.1007/978-1-84882-637-3_6
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DOI: https://doi.org/10.1007/978-1-84882-637-3_6
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