Peptide directoryHeart, vessels & kidneys

Endothelin-3

The endothelin of development, whose loss leaves the gut without nerves.

Where it comes from

Made in
The gut wall and skin before birth; brain, gut and kidney after
Sent out by
During the migration of neural crest cells into gut and skin
Acts on
  • Neural crest cells
  • Enteric neurons
  • Melanocytes

What it does

  • Guides the nerve cells of the gut and the pigment cells of the skin to their places 1
  • Signals through ETB in brain and kidney 3
  • A weak vasodilator through endothelial ETB, which is the receptor that also clears endothelin from the blood 3

In medicine

  • Mutations of EDN3 or its receptor cause Hirschsprung disease (a colon without nerves) and Waardenburg syndrome type 4, with a white forelock and deafness 1
  • Those mutations are rare. EDN3 and EDNRB together account for only a small share of Hirschsprung disease, most of which traces to RET 1
  • No medicine acts on it deliberately. Bosentan and macitentan block the ETB receptor it prefers, and whether that matters to the gut of an adult has never been studied 3

Beyond the body’s own use

  • In melanoma the ETB receptor helps the tumour spread, and blocking it slows melanoma cells in the laboratory; no endothelin blocker has shown benefit in a melanoma trial, and the current work is on antibodies that use the receptor as a target rather than block it 2
  • The same signal that places melanocytes before birth keeps them alive afterwards, which is why ETB turns up in work on greying hair and vitiligo; none of that has produced a treatment
  • Nothing is in trials, and endothelin-3 has no use beyond the laboratory: a peptide whose main job finishes before birth has little to offer an adult

Sources

  1. Edery et al., Mutation of the endothelin-3 gene in Waardenburg-Hirschsprung disease, Nature Genetics 1996
  2. Bagnato et al., Endothelin B receptor blockade inhibits cell interactions in melanoma cell progression, Cancer Research 2004
  3. Davenport et al., Update on endothelin receptor nomenclature, Pharmacological Reviews 2002

This card describes what a medicine is for and what the evidence says; it recommends nothing. Talk to your clinician about anything you read here.