Evidence for a 65 kDa sulfonylurea receptor in rat pancreatic zymogen granule membranes.
In rat pancreatic zymogen granules (ZG), a K+ selective conductance which can be blocked by ATP has been characterized. Here we show that this pathway can be specifically blocked by glibenclamide. Using a rapid filtration assay, we also found specific binding of [3H]glibenclamide to a low-affinity site (Kd 5.6 +/- 1.1 microM) in rat pancreatic zymogen granule membranes (ZGM). In photoaffinity labeling experiments with [3H]glibenclamide, a 65 +/- 1.5 kDa polypeptide was specifically labeled. Previously, a approximately 65 kDa mdr1 gene product has been demonstrated to be involved in the regulation of the K+ selective conductance of ZG. We conclude that this protein may be a subunit of, or associated with, a ZG K(ATP) channel.
Braun
M
M
II Department of Physiology, University of the Saarland, Homburg/Saar, Germany.
Anderie
I
I
Thévenod
F
F
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000345:Affinity Labels; D000818:Animals; D001665:Binding Sites; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004553:Electric Conductivity; D004591:Electrophoresis, Polyacrylamide Gel; D005905:Glyburide / Q000031:analogs & derivatives / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009711:Nucleotides / Q000494:pharmacology; D010179:Pancreas / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism*; D013053:Spectrophotometry; D064233:Sulfonylurea Receptors
D018528:ATP-Binding Cassette Transporters; D000345:Affinity Labels; D007004:Hypoglycemic Agents; D009711:Nucleotides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000255:Adenosine Triphosphate; D005905:Glyburide