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Effect of MgATP on pinacidil‐induced displacement of glibenclamide from the sulphonylurea receptor in a pancreatic β‐cell line and rat cerebral cortex
Author(s) -
Schwanstecher Mathias,
Brandt Christian,
Behrends Sönke,
Schaupp Ursula,
Panten Uwe
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14331.x
Subject(s) - glibenclamide , pinacidil , chemistry , diazoxide , receptor , sulfonylurea receptor , binding site , medicine , endocrinology , pharmacology , biophysics , biochemistry , insulin , biology , diabetes mellitus
1 The effects of blockers and openers of K + channels on binding of [ 3 H]‐glibenclamide to microsomes obtained from a pancreatic β‐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 μ m ) did not significantly displace [ 3 H]‐glibenclamide binding to microsomes from HIT‐cells. The displacement of [ 3 H]‐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 [ 3 H]‐glibenclamide binding to microsomes from rat cerebral cortex. 5 The effect of MgATP on pinacidil‐induced inhibition of [ 3 H]‐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.