Secretory mechanism of immunoreactive endothelin in cultured bovine endothelial cells

Biochem Biophys Res Commun. 1989 Apr 14;160(1):93-100. doi: 10.1016/0006-291x(89)91625-2.


To elucidate the cellular mechanism by which endothelin (ET) is secreted, we have studied the effects of a variety of vasoactive agents on the secretion of immunoreactive (IR)-ET from cultured bovine endothelial cells (EC). Confluent bovine EC cultured in serum-free medium secreted IR-ET as a function of time. Not only thrombin, but also vasoconstrictive hormones, such as arginine-vasopressin (AVP) and angiotensin (ANG) II, dose-dependently stimulated IR-ET secretion, and these effects were completely abolished by V1-receptor antagonist and [Sar1,Ala8]-ANG II, respectively. Protein kinase C (PKC)-activating phorbol ester and Ca2+ ionophore ionomycin had stimulatory effects on IR-ET secretion, and the combination of both compounds had a synergistic effect. These data suggest that AVP and ANG II, like thrombin, stimulate ET secretion from EC by a mechanism possibly involving receptor-mediated mobilization of intracellular Ca2+ and activation of PKC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology
  • Animals
  • Arginine Vasopressin / analogs & derivatives
  • Arginine Vasopressin / pharmacology
  • Carotid Arteries
  • Cattle
  • Cells, Cultured
  • Drug Synergism
  • Endothelins
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Ethers / pharmacology
  • Ionomycin
  • Kinetics
  • Peptides / metabolism*
  • Protein Kinase C / metabolism
  • Saralasin / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Thrombin / pharmacology


  • Endothelins
  • Ethers
  • Peptides
  • Angiotensin II
  • Arginine Vasopressin
  • Ionomycin
  • vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-
  • Protein Kinase C
  • Thrombin
  • Saralasin
  • Tetradecanoylphorbol Acetate