Endothelins--from receptors to medicine.
Since the discovery of endothelins, peptides with exceptional vasoconstrictor potency that were originally suggested to act by causing the opening of Ca2+ channels, it has emerged that these agents are important in intercellular communication in many tissues. They exert their effects through G protein-coupled receptors, of which two classes have been cloned. Robert Miller, John Pelton and John Huggins review the progress made towards a molecular understanding of ligand recognition by endothelin receptors. Receptor-selective agonists and antagonists have emerged from attempts to understand the three-dimensional structure of the endothelin pharmacophore, from structure-activity studies and from rapid-screening programmes. From the nature of the secretion and action of endothelins, it would seem that these peptides are involved in long-term changes rather than in acute responses to stimuli, and that they are likely to be important in a number of pathological states. Evidence suggests that receptor antagonists with appropriate affinity and selectivity may be useful in the treatment of conditions as diverse as hypertension, ulcerogenesis and ciclosporin toxicity.
Miller
R C
RC
Marion Merrell Dow Research Institute, Strasbourg, France.
Pelton
J T
JT
Huggins
J P
JP
D000595:Amino Acid Sequence; D000818:Animals; D016232:Endothelins / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D008969:Molecular Sequence Data; D017466:Receptors, Endothelin / Q000187:drug effects / Q000502:physiology*
D016232:Endothelins; D017466:Receptors, Endothelin