Identification of a domain of ETA receptor required for ligand binding.
Various chimeric ETA and ETB receptors were produced in CHO cells for the elucidation of a specific domain which influences the affinity of the receptor toward BQ-123, a selective ETA antagonist. Replacement of the first extracellular loop domain (B-loop) of the ETA receptor with the corresponding domain of the ETB receptor, reduced the inhibition by BQ-123 drastically, while the replacements of other extracellular domains of ETA did not. By contrast, the introduction of the B-loop of ETA in place of the corresponding domain of the ETB receptor endowed the ETB-based chimeric receptor with a sensitivity to BQ-123. These observations suggest that the B-loop domain of the ETA receptor is involved in ligand binding.
Adachi
M
M
Department of Molecular Genetics, Nippon Roche Research Center, Kamakura, Japan.
Yang
Y Y
YY
Trzeciak
A
A
Furuichi
Y
Y
Miyamoto
C
C
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D006224:Cricetinae; D016232:Endothelins / Q000378:metabolism; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000378:metabolism / Q000494:pharmacology; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017466:Receptors, Endothelin / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D014162:Transfection
D016232:Endothelins; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; D011993:Recombinant Fusion Proteins; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D002118:Calcium