MOLECULAR-CLONING OF HUMAN ENDOTHELIN (ET) RECEPTORS ET(A) AND ET(B)

Complementary DNAs coding for two different endothelin (ET) receptors were isolated from a human lung cDNA library. DNA sequencing revealed that they corresponded to either the ET-1-selective receptor subtype originally identified in cows (ET(A)) or the nonselective subtype first found in rats (ET(B)). An open reading frame coding for a 427 (ET(A)) or a 442 (ET(B)) amino acid-long protein, with a transmembrane topology also found in other G protein-coupled receptors, was determined. Whereas the amino acid identity is about 90% between the characterized members of a given receptor subtype, with the best conserved parts being the hydrophobic transmembrane domains, less than 60% identity was found between the human A and B subtypes. Southern blot analysis of human genomic DNA revealed the existence of multiple hybridizing bands when using probes derived from the full-length ET(A) or ET(B) cDNAs. However, when shorter fragments were selected as probes, only one band remained detectable, which suggests the existence of a single-copy gene for each subtype of ET receptor.