Shared determinants of receptor binding for subtype selective, and dual endothelin-angiotensin antagonists on the AT1 angiotensin II receptor.

Site-directed interspecies amino acid exchange was used to compare the binding determinants of a novel dual endothelial-angiotensin receptor ligand, L-746,072, with type-1 angiotensin receptor (AT1) selective antagonists on AT receptors expressed in COS cells. These studies suggest that residues on AT receptors which are non-conserved between amphibian and mammalian species play a greater role in subtype selective ligand recognition than for dual receptor ligands. These data also support the hypothesis that a common non-peptide binding site exists within transmembrane domains on peptidergic receptors.