Endothelin receptor type B

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.^[6]

In melanocytic cells the EDNRB gene is regulated by the microphthalmia-associated transcription factor. Mutations in either gene are links to Waardenburg syndrome.^[7][8]

The multigenic disorder, Hirschsprung disease type 2, is due to mutation in endothelin receptor type B gene.^[9]

In horses, a mutation in the middle of the EDNRB gene, Ile118Lys, when homozygous, causes Lethal White Syndrome.^[10] In this mutation, a mismatch in the DNA replication causes lysine to be made instead of isoleucine.^[10] The resulting EDNRB protein is unable to fulfill its role in the development of the embryo, limiting the migration of the melanocyte and enteric neuron precursors. A single copy of the EDNRB mutation, the heterozygous state, produces an identifiable and completely benign spotted coat color called frame overo.^[11]

Endothelin receptor type B has been shown to interact with Caveolin 1.^[12]

Agonists

• IRL-1620^[13]

Antagonists

• A-192,621
• BQ-788
• Bosentan (unselective ET_A / ET_B antagonist)

• Endothelin receptor