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 [H-3]glibenclamide to a low-affinity site (K-d 5.6 +/- 1.1 mu M) in rat pancreatic zymogen granule membranes (ZGM). In photoaffinity labeling experiments with [H-3]glibenclamide, a 65 +/- 1.5 kDa polypeptide was specifically labeled. Previously, a similar to 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. (C) 1997 Federation of European Biochemical Societies.