Endothelin receptor type B

Function

Endothelin receptor type B is a G protein-coupled receptor which activates a phosphatidylinositol-calcium second messenger system. Its ligand, endothelin, consists of a family of three potent vasoactive peptides: ET1, ET2, and ET3. A splice variant, named SVR, has been described; the sequence of the ETB-SVR receptor is identical to ETRB except for the intracellular C-terminal domain. While both splice variants bind ET1, they exhibit different responses upon binding which suggests that they may be functionally distinct.

Regulation

In melanocytic cells the EDNRB gene is regulated by the microphthalmia-associated transcription factor. Mutations in either gene are links to Waardenburg syndrome.

Clinical significance

The multigenic disorder, Hirschsprung disease type 2, is due to mutation in endothelin receptor type B gene.

Animals

In horses, a mutation in the middle of the EDNRB gene, Ile118Lys, when homozygous, causes Lethal White Syndrome. In this mutation, a mismatch in the DNA replication causes lysine to be made instead of isoleucine.

Interactions

Endothelin receptor type B has been shown to interact with Caveolin 1.

Ligands

; Agonists

• IRL-1620

; Antagonists

• A-192,621
• BQ-788
• Bosentan (unselective ETA / ETB antagonist)

References

References

1. (Nov 1991). "Cloning and chromosomal localization of a human endothelin ETA receptor". Biochemical and Biophysical Research Communications.
2. "Entrez Gene: EDNRB endothelin receptor type B".
3. (Apr 2008). "Epistatic connections between microphthalmia-associated transcription factor and endothelin signaling in Waardenburg syndrome and other pigmentary disorders". FASEB Journal.
4. (Dec 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research.
5. (May 1998). "Novel mutations of the endothelin B receptor gene in patients with Hirschsprung's disease and their characterization". The Journal of Biological Chemistry.
6. (Jun 1998). "A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease". Human Molecular Genetics.
7. (1998). "A missense mutation in the endothelin-B receptor gene is associated with Lethal White Foal Syndrome: an equine version of Hirschsprung disease". Mamm. Genome.
8. (Apr 2003). "Regulated interaction of endothelin B receptor with caveolin-1". European Journal of Biochemistry.
9. (Dec 2014). "Endothelin@25 - new agonists, antagonists, inhibitors and emerging research frontiers: IUPHAR Review 12". British Journal of Pharmacology.