EFFECT OF MGATP ON PINACIDIL-INDUCED DISPLACEMENT OF GLIBENCLAMIDE FROM THE SULFONYLUREA RECEPTOR IN A PANCREATIC BETA-CELL LINE AND RAT CEREBRAL-CORTEX

1 The effects of blockers and openers of K+ channels on binding of [H-3]-glibenclamide to microsomes obtained from a pancreatic beta-cell line (HIT-T15) or rat cerebral cortex were examined. 2 The blockers quinine, chlorpromazine and thiopentone and the openers cromakalim [(+/-) 6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidyl)-2H-benzo[b]pyran-3-ol] and minoxidil sulphate did not significantly interact with the sulphonylurea receptor of HIT-cells both at phosphorylating (presence of MgATP) and dephosphorylating (absence of MgATP) conditions. 3 In the absence of MgATP, pinacidil (200- 500-mu-m) did not significantly displace [H-3]-glibenclamide binding to microsomes from HIT-cells. The displacement of [H-3]-glibenclamide binding was strongly enhanced by MgATP and was due to a decrease in the number of high affinity binding sites for glibenclamide. 4 MgATP enhanced pinacidil-induced inhibition of [H-3]-glibenclamide binding to microsomes from rat cerebral cortex. 5 The effect of MgATP on pinacidil-induced inhibition of [H-3]-glibenclamide binding was maintained after solubilization of the membranes from HIT-cells or rat cerebral cortex. 6 It is concluded that the sulphonylurea receptor is regulated not only by sulphonylureas but also by the K+ channel openers, diazoxide and pinacidil, and by protein phosphorylation. The binding sites for sulphonylureas and these K+ channel openers are not identical, but appear to be located at a single protein or at tightly associated proteins.