Endothelin Receptors

In 1988, a 21-amino acid endothelium-derived bioactive peptide was cloned and named endothelin (ET)¹. Later, two other isoforms differing from the original ET-1 in two or six residues, respectively, were cloned and named ET-2 and ET-3². All endothelins bear the common structure with two disulfide links . ETs are among the most powerful vasoconstrictive substances known today. They also act as growth factors involved in fetal development and vascular regulation⁵.

Two types of endothelin receptors have been cloned and named ET-A³ and ET-B⁴. The two classes differ in their affinity to different ETs. ET-A has a stronger affinity to ET-1 (ET-1>ET-2>> ET-3), while ET-B has an equal affinity towards all the three ETs. Both the ET-A and ET-B are G-protein-coupled receptors with extracellular N-termini, 7 transmembrane domains and intracellular C-termini. They share ~60% homology.

References

1. Yanagisawa, M. et al. (1988) Nature 332, 411.
2. Inoue, A. et al. (1989) Proc. Natl. Acad. Sci. USA 86, 2863.
3. Arai, H. et al. (1990) Nature 348, 730.
4. Sakurai, T. et al. (1990) Nature 348, 732.
5. Stjernquist, M. et al. (1998) Cell Tissue Res. 292, 1.