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.