Identification of the ET(A) receptor subtype that mediates endothelin induced autocrine proliferation of normal human keratinocytes

A. Bagnato, A. Venuti, V. Di Castro, M. L. Marcante

Research output: Contribution to journalArticle

Abstract

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 ET receptor subtype (BQ 123) inhibited DNA syntesis stimulated by ET-1 and reduced the basal growth rate of unstimulated cells. These data suggest that the ET-1 induced DNA syntesis is mediated by ET(A) receptor subtype and that endogenously produced ET-1 promotes the autocrine proliferation of keratinocytes.

Original languageEnglish
Pages (from-to)80-86
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume209
Issue number1
DOIs
Publication statusPublished - 1995

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ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology
  • Cell Biology

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