Modification of the mitochondrial sulfonylurea receptor by thiol reagents

Biochem Biophys Res Commun. 1999 Aug 19;262(1):255-8. doi: 10.1006/bbrc.1999.1190.

Abstract

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 [(3)H]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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters*
  • Adenosine Diphosphate / pharmacology
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Binding Sites / drug effects
  • Cattle
  • Dithionitrobenzoic Acid / pharmacology
  • Dose-Response Relationship, Drug
  • Ethylmaleimide / metabolism
  • Ethylmaleimide / pharmacology
  • Glyburide / metabolism
  • Hydrogen Peroxide / pharmacology
  • Intracellular Membranes / drug effects
  • Intracellular Membranes / metabolism
  • Kinetics
  • Mersalyl / pharmacology
  • Mitochondria, Heart / drug effects*
  • Mitochondria, Heart / metabolism
  • Oxidants / pharmacology
  • Permeability
  • Potassium Channels / metabolism*
  • Potassium Channels, Inwardly Rectifying*
  • Receptors, Drug / metabolism*
  • Reducing Agents / pharmacology
  • Sulfhydryl Compounds / metabolism
  • Sulfhydryl Reagents / pharmacology*
  • Sulfonylurea Receptors

Substances

  • ATP-Binding Cassette Transporters
  • Oxidants
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Reducing Agents
  • Sulfhydryl Compounds
  • Sulfhydryl Reagents
  • Sulfonylurea Receptors
  • Mersalyl
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Dithionitrobenzoic Acid
  • Hydrogen Peroxide
  • Ethylmaleimide
  • Glyburide