Endothelin-1-selective binding sites are downregulated by transforming growth factor-beta and upregulated by basic fibroblast growth factor in a vascular smooth muscle-derived cell line

J Cardiovasc Pharmacol. 1994 Jun;23(6):988-94. doi: 10.1097/00005344-199406000-00018.

Abstract

Endothelins (ETs) elicit in vivo and in vitro a potent vasoconstrictor activity after binding to high-affinity receptors on vascular smooth muscle cells (VSMC). A617 cells, a VSM-derived cell line, were used as an in vitro model system to study selected growth factors and cytokines involved in proliferative and/or inflammatory diseases of the vessel wall as possible regulators of the high-affinity binding capacity of ET-1 to the cells. Radioligand studies characterized the binding of ET-1 to the isopeptide selective ETA receptor subtype on A617 cells as a time- and temperature-dependent saturable process (Kd = 0.13 +/- 0.04 nM, Bmax = 49 +/- 7 fmol/10(6) cells). Pretreatment of A617 cells with basic fibroblast growth factor (bFGF), a mitogenic agent for vascular cells, resulted in a time- and dose-dependent increase in ET-1 binding capacity, whereas preexposure to transforming growth factor-beta (TGF-beta) induced a reduction of the Bmax for ET-1. Platelet-derived growth factor (PDGF), interleukin-6 (IL-6), tumor necrosis factor-alpha, and fetal bovine serum (FBS) pretreatments did not affect consequent ET-1 binding to A617 cells.

MeSH terms

  • Binding Sites
  • Cells, Cultured
  • Cytokines / pharmacology
  • Down-Regulation / drug effects*
  • Endothelins / metabolism*
  • Fibroblast Growth Factor 2 / pharmacology*
  • Growth Substances / pharmacology
  • Humans
  • Iodine Radioisotopes
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism*
  • Receptors, Endothelin / drug effects*
  • Receptors, Endothelin / metabolism*
  • Transforming Growth Factor beta / pharmacology*
  • Up-Regulation / drug effects*

Substances

  • Cytokines
  • Endothelins
  • Growth Substances
  • Iodine Radioisotopes
  • Receptors, Endothelin
  • Transforming Growth Factor beta
  • Fibroblast Growth Factor 2