Endothelins are among the most potent vasoconstrictor proteins known. Overexpression of endothelins contributes to hypertension and heart disease. Three isoforms are known, each containing 21 amino acids: endothelin-1 (ET-1), endothelin-2 (ET-2), and endothelin-3 (ET-3). All three isoforms are encoded by a 38-amino-acid precursor known as big endothelin. Recently, 31-amino acid endothelins were discovered. These ET (1-31) proteins are generated by specific cleavage of big endothelin by human chymase. Endothelins are expressed in many tissues, including lung, kidney, brain, pituitary, and placenta. Overexpression of endothelins contributes to hypertension and heart disease. Endothelins mediate their activity through binding to two distinct endothelin receptors, known as endothelin A receptor and endothelin B receptor.
ET-1 is produced by vascular endothelial cells. Overexpression of ET-1 contributes to hypertension and heart disease, and also has effects on the central nervous system. ET-1 is also known as PPET1 and HDLCQ7.
The processed form of ET-2 binds to several endothelin receptors that initiate intracellular signaling events and control a range of processes, including hypertension and ovulation. ET-2 is also known as PPET2.
The active form of ET-3 is a ligand for endothelin receptor type B (EDNRB). This interaction is essential for development of neural crest-derived cell lineages, such as melanocytes and enteric neurons. Mutations in the ET-3 gene are associated with the congenital disorders Hirschsprung disease (HSCR) and Waardenburg syndrome (WS). Endothelin-3 is also known as PPET3, HSCR4, and WS4B.
The endothelin A receptor, encoded by the EDNRA gene, associates with guanine-nucleotide-binding (G) proteins; this interaction activates a phosphatidylinositol-calcium second messenger system. Endothelin A receptor binds ET-1 with high affinity and ET-2 with moderate affinity. It binds very weakly to ET-3. Endothelin A receptor is expressed in a variety of tissues, including lung, aorta, atrium, liver, muscle, cerebral cortex, cerebellum, kidney, adrenal, duodenum, colon, and placenta. Endothelin A receptor is also known as endothelin receptor type A, ET-A, ETA-R, ETRA, hET-AR, and ET-1 receptor.
The endothelin B receptor, encoded by the EDNRB gene, associates with guanine-nucleotide-binding (G) proteins; this interaction activates a phosphatidylinositol-calcium second messenger system. Endothelin B receptor binds ET-1 and ET-3 with high affinity. It is expressed in endothelial cells lining the wall of all blood vessels, and in lung, brain, and heart. Mutations in the EDRNB gene are linked to Waardenburg syndrome and Hirschsprung disease type 2. The endothelin B receptor is also known as endothelin receptor type B, ET-B, ETBR, ETRB, hET-BR, HSCR, HSCR2, ABCDS, and endothelin receptor nonselective type.
ELISAs for Endothelin Detection
These kits are solid-phase sandwich ELISAs using two antibodies that are highly specific to ET-1(1-21), ET-1 (1-31), human ET-2 (1-31), or human ET-3 protein; one is precoated on the ELISA plate, and the other is HRP-conjugated. These kits can be used to measure soluble ET-1 (1-21), ET-1 (1-31), human ET-2 (1-31), or human ET-3 protein in serum, EDTA-plasma, cell culture supernatants, or tissue extracts.
Antibodies for Endothelin Detection
This suite of affinity-purified IgG antibody products recognizes the following: human endothelin A or B receptors; human, bovine, canine, mouse, porcine, and rat ET-1; human, mouse, and rat ET-3; or human ET-1, ET-2, and ET-3. The antibodies were raised in rabbit or mouse using a synthetic peptide or recombinant protein and can be used for Western blot (WB) detection or immunohistochemical (IHC) detection.
