Endothelin-1 activation of ETB receptors leads to a reduced cellular proliferative rate and an increased cellular footprint

Exp Cell Res. 2012 Jun 10;318(10):1125-33. doi: 10.1016/j.yexcr.2012.03.029. Epub 2012 Apr 4.


Endothelin-1 (ET-1) is a vasoactive peptide which signals through two G-protein coupled receptors, endothelin receptor A (ETA) and B (ETB). We determined that ET-1 activation of its ETB receptor in stably cDNA transfected CHO cells leads to a 55% reduction in cell number by end-point cell counting and a 35% decrease in cell growth by a real-time cell-substrate impedance-based assay after 24h of cell growth. When CHO ETB cells were synchronized in the late G1 cell cycle phase, ET-1 delayed their S phase progression compared to control by 30% as determined by [(3)H]-thymidine incorporation. On the other hand, no such delay was observed during late G2/M to G1 transit when cells were treated with ET-1 after release from mitotic arrest. Using the cell-substrate impedance-based assay, we observed that ET-1 induces opposing morphological changes in CHO ETA and CHO ETB cells with ETB causing an increase in the cell footprint and ETA a decrease. Likewise, in pulmonary artery smooth muscle cells, which express both ETA and ETB receptors, ET-1 induces an ETA-dependent contraction and an ETB dependent dilation. These results are shedding light on a possible beneficial role for ETB in diseases involving ET-1 dysfunction such as pulmonary hypertension.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CHO Cells
  • Cell Count
  • Cell Cycle
  • Cell Proliferation*
  • Cell Shape / drug effects
  • Cricetinae
  • DNA / biosynthesis
  • Electric Impedance
  • Endothelin B Receptor Antagonists
  • Endothelin-1 / physiology*
  • Humans
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / physiology
  • Oligopeptides / pharmacology
  • Piperidines / pharmacology
  • Pulmonary Artery / cytology
  • Receptor, Endothelin A / metabolism
  • Receptor, Endothelin B / agonists
  • Receptor, Endothelin B / metabolism*
  • Signal Transduction


  • Endothelin B Receptor Antagonists
  • Endothelin-1
  • Oligopeptides
  • Piperidines
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • BQ 788
  • DNA