EVIDENCE FOR A 65 KDA SULFONYLUREA RECEPTOR IN RAT PANCREATIC ZYMOGENGRANULE MEMBRANES

In rat pancreatic zymogen granules (ZG), a K+ selective conductance wh ich can be blocked by ATP has been characterized, Here we show that th is pathway can be specifically blocked by glibenclamide, Using a rapid filtration assay, we also found specific binding of [H-3]glibenclamid e to a low-affinity site (K-d 5.6 +/- 1.1 mu M) in rat pancreatic zymo gen granule membranes (ZGM). In photoaffinity labeling experiments wit h [H-3]glibenclamide, a 65 +/- 1.5 kDa polypeptide was specifically la beled. Previously, a similar to 65 kDa mdr1 gene product has been demo nstrated to be involved in the regulation of the K+ selective conducta nce of ZG, We conclude that this protein may be a subunit of, or assoc iated with, a ZG K-ATP channel. (C) 1997 Federation of European Bioche mical Societies.