title: Anatomical localization and pharmacological activity of mature endothelins and their precursors in human vascular tissue.
abstract: OBJECTIVE
  We developed four selective rabbit antisera in order to compare the distribution of immunoreactive mature endothelins and their precursors, proendothelin-1, proendothelin-2 and proendothelin-3, in the endothelium from human vascular tissue. Our second aim was to use in vitro pharmacological assays to test the vasoconstrictor actions of the mature endothelin and proendothelin peptides.
  
  
  METHODS
  The antisera were shown to be selective by enzyme-linked immunosorbent assays. With these antisera, we detected immunoreactivity in serial cryostat sections from saphenous and mesenteric veins, and mesenteric and internal mammary arteries, using a peroxidase-antiperoxidase technique. In pharmacological experiments, segments of human coronary and mesenteric arteries were exposed to cumulative (0.06-60 nmol/l) concentrations of the endothelins and their precursors.
  
  
  RESULTS
  Antisera directed against mature endothelin stained the cytoplasm of endothelial cells in all vessels tested. Immunoreactive proendothelin-1 and proendothelin-2 were also detected, but not proendothelin-3. Endothelin-1 and endothelin-2 were strongly vasoactive, with similar molar potencies, and caused a dose-related increase in contractile force in human coronary arteries (0.06-60 nmol/l). However, proendothelin-1 and proendothelin-2 were 100-fold and 1000-fold less vasoactive than their respective mature peptides. No contractile effect was seen with proendothelin-3 or endothelin-3 at the concentrations tested in human coronary arteries, and similar results were obtained with human mesenteric arteries.
  
  
  CONCLUSIONS
  These results suggest that proendothelin-1 and proendothelin-2 must be converted to their corresponding mature peptides to produce vasoconstrictor activity in human vessels. Immunoreactive mature endothelin is widely distributed in human vascular endothelial cells and, if released, may produce endothelin-mediated vasoconstriction.
authors.affiliation: Clinical Pharmacology Unit, University of Cambridge, UK.
authors.forename: P G
authors.initials: PG
authors.lastname: Howard
authors.forename: C
authors.initials: C
authors.lastname: Plumpton
authors.forename: A P
authors.initials: AP
authors.lastname: Davenport
mesh_terms: D003331:Coronary Vessels / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D004730:Endothelium, Vascular / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000502:physiology; D010446:Peptide Fragments / Q000737:chemistry / Q000502:physiology*; D011498:Protein Precursors / Q000737:chemistry / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D016232:Endothelins; D010446:Peptide Fragments; D011498:Protein Precursors; C078162:proendothelin 2; C078163:proendothelin 3; C079212:proendothelin-1 (31-38)