Endothelin Receptors and Their Antagonists
Seminars in Nephrology
MetadataShow full item record
Maguire, J., & Davenport, A. (2015). Endothelin Receptors and Their Antagonists. Seminars in Nephrology, 35 125-136. https://doi.org/10.1016/j.semnephrol.2015.02.002
All three members of the endothelin (ET) family of peptides, ET-1, ET-2, and ET-3, are expressed in the human kidney, with ET-1 being the predominant isoform. ET-1 and ET-2 bind to two G-protein–coupled receptors, ETA and ETB, whereas at physiological concentrations ET-3 has little affinity for the ETA receptor. The human kidney is unusual among the peripheral organs in expressing a high density of ETB. The renal vascular endothelium only expresses the ETB subtype and ET-1 acts in an autocrine or paracrine manner to release vasodilators. Endothelial ETB in kidney, as well as liver and lungs, also has a critical role in scavenging ET-1 from the plasma. The third major function is ET-1 activation of ETB in in the nephron to reduce salt and water re-absorption. In contrast, ETA predominate on smooth muscle, causing vasoconstriction and mediating many of the pathophysiological actions of ET-1. The role of the two receptors has been delineated using highly selective ETA (BQ123, TAK-044) and ETB (BQ788) peptide antagonists. Nonpeptide antagonists, bosentan, macitentan, and ambrisentan, that are either mixed ETA/ETB antagonists or display ETA selectivity, have been approved for clinical use but to date are limited to pulmonary hypertension. Ambrisentan is in clinical trials in patients with type 2 diabetic nephropathy. This review summarizes ET-receptor antagonism in the human kidney, and considers the relative merits of selective versus nonselective antagonism in renal disease.
Ambrisentan, antagonist, bosentan, endothelin-1, macitentan, sitaxentan
Supported by the British Heart Foundation (PS/02/001, PG/05/127/19872, FS/12/64/130001), Wellcome Trust Programme in Metabolic and Cardiovascular Disease 096822/Z/11/Z, National Institute for Health Research Cambridge Bio-medical Research Centre, and the Pulmonary Hypertension Association United Kingdom.
Wellcome Trust (096822/Z/11/Z)
BRITISH HEART FDN (PG/05/127/19872)
External DOI: https://doi.org/10.1016/j.semnephrol.2015.02.002
This record's URL: https://www.repository.cam.ac.uk/handle/1810/247745
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/
Recommended or similar items
The following licence files are associated with this item: