Modification of the mitochondrial sulfonylurea receptor by thiol reagents.
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.
Szewczyk
A
A
Nencki Institute of Experimental Biology, 3 Pasteur St., Warsaw, 02-093, Poland. adam@nencki.gov.pl
Wójcik
G
G
Lobanov
N A
NA
Nalecz
M J
MJ
D018528:ATP-Binding Cassette Transporters; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002417:Cattle; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005033:Ethylmaleimide / Q000378:metabolism / Q000494:pharmacology; D005905:Glyburide / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008634:Mersalyl / Q000494:pharmacology; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D010539:Permeability; D015221:Potassium Channels / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug / Q000378:metabolism*; D019163:Reducing Agents / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013439:Sulfhydryl Reagents / Q000494:pharmacology*; D064233:Sulfonylurea Receptors
D018528:ATP-Binding Cassette Transporters; D016877:Oxidants; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D019163:Reducing Agents; D013438:Sulfhydryl Compounds; D013439:Sulfhydryl Reagents; D064233:Sulfonylurea Receptors; D008634:Mersalyl; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D004228:Dithionitrobenzoic Acid; D006861:Hydrogen Peroxide; D005033:Ethylmaleimide; D005905:Glyburide