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.
Dascal
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Department of Medicine, Georgetown University Medical Center, Washington, DC 20007, USA.
Nirula
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V
Lawus
K
K
Yoo
S E
SE
Walsh
T F
TF
Sandberg
K
K
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
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