title: Shared determinants of receptor binding for subtype selective, and dual endothelin-angiotensin antagonists on the AT1 angiotensin II receptor.
abstract: 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.
authors.affiliation: Department of Medicine, Georgetown University Medical Center, Washington, DC 20007, USA.
authors.forename: D
authors.initials: D
authors.lastname: Dascal
authors.forename: V
authors.initials: V
authors.lastname: Nirula
authors.forename: K
authors.initials: K
authors.lastname: Lawus
authors.forename: S E
authors.initials: SE
authors.lastname: Yoo
authors.forename: T F
authors.initials: TF
authors.lastname: Walsh
authors.forename: K
authors.initials: K
authors.lastname: Sandberg
mesh_terms: D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D065128:Endothelin Receptor Antagonists; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008969:Molecular Sequence Data; D015394:Molecular Structure; D016297:Mutagenesis, Site-Directed; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000737:chemistry / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D057911:Angiotensin Receptor Antagonists; D065128:Endothelin Receptor Antagonists; D007093:Imidazoles; D008024:Ligands; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II