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Endothelin.

Anthony P Davenport1, Kelly A Hyndman2, Neeraj Dhaun2

  • 1Experimental Medicine and Immunotherapeutics, University of Cambridge, Cambridge, United Kingdom (A.P.D., J.J.M.); IUPHAR/BPS Guide to PHARMACOLOGY, Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, Edinburgh, United Kingdom (C.S.); Division of Nephrology, University of Utah Health Sciences Center, Salt Lake City, Utah (D.E.K.); Cardio-Renal Physiology & Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama (K.A.H., J.S.P., D.M.P.); and Department of Renal Medicine, Royal Infirmary of Edinburgh (N.D.) and University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute (D.J.W.N.D.), Edinburgh, Scotland, United Kingdom apd10@medschl.cam.ac.uk.

Pharmacological Reviews
|March 10, 2016
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Summary
This summary is machine-generated.

Endothelin peptides regulate cardiovascular function and have led to new treatments for pulmonary arterial hypertension. Further research into endothelin signaling pathways may reveal novel therapeutic targets for various diseases.

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Area of Science:

  • Cardiovascular Physiology
  • Pharmacology
  • Molecular Biology

Background:

  • Endothelins are 21-amino acid peptides with vital roles in vertebrate physiology.
  • The endothelin ligand-receptor signaling pathway is a vertebrate innovation, with endothelin-1 being a potent vasoconstrictor.

Purpose of the Study:

  • To review the pharmacology of endothelins and their receptors (ETA and ETB).
  • To discuss the therapeutic applications and ongoing research of endothelin antagonists and agonists.

Main Methods:

  • Utilized selective peptide ETA and ETB antagonists and ETB agonists.
  • Reviewed clinical trials and translational studies.
  • Examined genetic modifications in the endothelin system in mice.

Main Results:

  • Endothelin antagonists have significantly improved pulmonary arterial hypertension treatment.
  • ETB agonists show potential in chemotherapy and neuroprotection.
  • Genetic studies have identified key roles for endothelin isoforms in physiological functions.

Conclusions:

  • The endothelin system offers promising therapeutic targets for various conditions.
  • Novel pharmacological strategies, including epigenetic modulators and monoclonal antibodies, are emerging.