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The binding site for [ 3 H]glibenclamide in the rat cerebral cortex does not recognize K‐channel agonists or antagonists other than sulphonylureas
Author(s) -
Angel I.,
Bidet S.
Publication year - 1991
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1991.tb00704.x
Subject(s) - glibenclamide , pinacidil , chemistry , chlorpropamide , cromakalim , quinidine , apamin , binding site , diazoxide , agonist , pharmacology , endocrinology , medicine , potassium channel , biochemistry , receptor , insulin , diabetes mellitus
Summary— The binding of the potent oral antidiabetic sulphonylurea [ 3 H]glibenclamide was studied in rat cerebral cortex membranes. A single population of high affinity and saturable binding sites with equilibrium constants, K d = 0.2 ± 0.06 nM and B max = 58.6 ± 6.2 fmol/mg protein was found. Specific [ 3 H]glibenclamide binding to rat cerebral cortex membranes was inhibited by glibenclamide and other sulphonylureas, glibenclamide being the most potent drug and the sulphonylurea of the second generation chlorpropamide the least potent. This observation suggests that this site may be related to the hypoglycaemic properties of sulphonylureas and possibly to their interaction with ATP‐sensitive K+‐channel. Nevertheless, other non‐selective K+‐channel antagonists such as TEA, 4‐aminopyridine, quinine, quinidine or apamin failed to interact with this site (IC 50 > 100 μM). Similarly, both non‐selective K+‐channel agonists such as cromakalim, pinacidil or minoxidil as well as the pancreatic ATP‐sensitive K+‐channel agonist diazoxide failed to interact with this site. It may thus be concluded that this site, under the present experimental conditions, represents a drug specific recognition site which may be coupled to the hypoglycaemic activity of sulphonylureas, possibly on a particulate ATP‐dependent K+‐channel.