Modification of the Mitochondrial Sulfonylurea Receptor by Thiol Reagents

• Published in: Biochemical and biophysical research communications Vol. 262; no. 1; pp. 255 - 258
• Main Authors: Szewczyk, Adam, Wójcik, Grażyna, Lobanov, Nikolai A., Nałęcz, Maciej J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.08.1999
• Subjects: Adenosine Diphosphate - pharmacology; Adenosine Triphosphate - pharmacology; Animals; ATP-Binding Cassette Transporters; Binding Sites - drug effects; Cattle; Dithionitrobenzoic Acid - pharmacology; Dose-Response Relationship, Drug; Ethylmaleimide - metabolism; Ethylmaleimide - pharmacology; glibenclamide; Glyburide - metabolism; Hydrogen Peroxide - pharmacology; Intracellular Membranes - drug effects; Intracellular Membranes - metabolism; Kinetics; Mersalyl - pharmacology; mitochondria; Mitochondria, Heart - drug effects; Mitochondria, Heart - metabolism; mitochondrial sulfonylurea receptor; Oxidants - pharmacology; Permeability; Potassium Channels - metabolism; Potassium Channels, Inwardly Rectifying; Receptors, Drug - metabolism; Reducing Agents - pharmacology; SH reagents; Sulfhydryl Compounds - metabolism; Sulfhydryl Reagents - pharmacology; Sulfonylurea Receptors; SH reagents; glibenclamide; mitochondrial sulfonylurea receptor; mitochondria
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1999.1190

The purpose of this study was to investigate the effects exerted by thiol-modifying reagents on themitochondrial sulfonylurea receptor. The thiol-oxidizing agents (timerosal and 5,5′-dithio-bis(2-nitrobenzoic acid)) were found to produce a large inhibition (70% to 80%) of specific binding of [3H]glibenclamide to the beef heart mitochondrial membrane. Similar effects were observed with membrane permeable (N-ethylmaleimide) and non-permeable (mersalyl) thiol modifying agents. Glibenclamide binding was also decreased by oxidizing agents (hydrogen peroxide) but not by reducing agents (reduced gluthatione, dithiothreitol and the 2,3-dihydroxy-1,4-dithiolbutane). The results suggest that intact thiol groups, facing the mitochondrial matrix, are essential for glibenclamide binding to the mitochondrial sulfonylurea receptor.