Evidence for a 65 kDa sulfonylurea receptor in rat pancreatic zymogen granule membranes

FEBS Lett. 1997 Jul 14;411(2-3):255-9. doi: 10.1016/s0014-5793(97)00711-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters*
  • Adenosine Triphosphate / pharmacology
  • Affinity Labels
  • Animals
  • Binding Sites
  • Carbonyl Cyanide m-Chlorophenyl Hydrazone / pharmacology
  • Cytoplasmic Granules / metabolism*
  • Electric Conductivity
  • Electrophoresis, Polyacrylamide Gel
  • Glyburide / analogs & derivatives
  • Glyburide / pharmacology
  • Hypoglycemic Agents / pharmacology
  • Intracellular Membranes / metabolism
  • Male
  • Nucleotides / pharmacology
  • Pancreas / metabolism*
  • Potassium Channel Blockers
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism*
  • Potassium Channels / physiology
  • Potassium Channels, Inwardly Rectifying*
  • Protein Binding
  • Rats
  • Rats, Wistar
  • Receptors, Drug / drug effects
  • Receptors, Drug / metabolism*
  • Spectrophotometry
  • Sulfonylurea Receptors

Substances

  • ATP-Binding Cassette Transporters
  • Affinity Labels
  • Hypoglycemic Agents
  • Nucleotides
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Sulfonylurea Receptors
  • Carbonyl Cyanide m-Chlorophenyl Hydrazone
  • Adenosine Triphosphate
  • Glyburide