Identification of the ETA receptor subtype that mediates endothelin induced autocrine proliferation of normal human keratinocytes

Biochem Biophys Res Commun. 1995 Apr 6;209(1):80-6. doi: 10.1006/bbrc.1995.1473.


Endothelin-1 has a wide range of pharmacological effects in various tissues and acts as autocrine/paracrine factor. The potential of ET-1 to function as an autocrine growth factor was evaluated in normal human keratinocytes. Radioligand binding studies showed that 125I-ET-1 bound to a single class of high-affinity-binding sites on the surface of the cells. The dissociation constant was 0.045 nM with receptor numbers of 1700 sites/cell. Treatment with serum caused increases in expression of binding sites (3500 sites/cell), with no change in binding affinity. ET-1 stimulated thymidine incorporation in these cells that expressed ET receptors. An ET antagonist selective for the ETA receptor subtype (BQ 123) inhibited DNA synthesis stimulated by ET-1 and reduced the basal growth rate of unstimulated cells. These data suggest that the ET-1 induced DNA synthesis is mediated by ETA receptor subtype and that endogenously produced ET-1 promotes the autocrine proliferation of keratinocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Division / drug effects
  • Cells, Cultured
  • Endothelin Receptor Antagonists
  • Endothelins / pharmacology*
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / drug effects*
  • Peptides, Cyclic / pharmacology
  • Receptor, Endothelin A
  • Receptors, Endothelin / metabolism*


  • Endothelin Receptor Antagonists
  • Endothelins
  • Peptides, Cyclic
  • Receptor, Endothelin A
  • Receptors, Endothelin
  • cyclo(Trp-Asp-Pro-Val-Leu)