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Endothelin‐receptor interactions
Author(s) -
Spinella Michael J.,
Kottke Rebecca,
Magazine Harold I.,
Healy Matthew S.,
Catena John A.,
Wilken Philip,
Andersen Thomas T.
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)80970-6
Subject(s) - receptor , chemistry , endothelin receptor , binding site , alkylation , disulfide bond , radioligand assay , biochemistry , ligand (biochemistry) , mechanism of action , stereochemistry , biophysics , biology , in vitro , catalysis
The mechanism of action of endothelin‐receptor interactions was studied, using radioligand binding assays and SDS‐PAGE, to investigate the possibility of disulfide interchange. Electrophoretic analysis suggested involvement of disulfide bond(s) in the receptor‐ligand complex. Treatment of Et receptors with sulfhydryl‐specific alkylating reagents (NEM or others) resulted in decreased ability to bind [ 125 I]Et‐1. [Dpr 1 ‐Asp 15 ]Et‐1, an antagonist homologous to Et but with an amide link replacing one of the disulfides, bound to Et receptors reversibly, but binding of Et‐1 was less reversible. Preincubation of receptors with Et‐L, but not with [Dpr 1 ‐Asp 15 ]Et‐L, protected receptors from alkylation with [ 14 C]NEM. The data suggest that the Et receptor has a sulfhydryl group at or near the Et binding site. A model is proposed in which the role of the putative sulfhydryl group is discussed.