Pharmacological characterization of the sulphonylurea receptor in rat isolated aorta

The binding of the sulphonylurea [3H]-glibenclamide, a blocker of adenosine 5′-triphosphate (ATP)-sensitive K+ channels (KATP channels), was studied in endothelium-denuded rings from rat aorta. [3H]-glibenclamide labelled two classes of binding sites with KD values of 20±5 nM and 32±1 μM. The high affinity component, which comprised 17% of total binding at 1 nM [3H]-glibenclamide, had an estimated binding capacity of 150 fmol mg−1 wet weight. Other sulphonylureas such as glipizide and glibornuride and the sulphonylurea-related carboxylate, AZ-DF 265, inhibited high affinity [3H]-glibenclamide binding with the potencies expected from their K+ channel activity. At very high concentrations, AZ-DF 265 and glipizide started to interact also with the low affinity component of [3H]-glibenclamide binding. Openers of the ATP-sensitive K+ channel belonging to different structural groups inhibited only the high affinity [3H]-glibenclamide binding; the potencies in this assay were similar to those obtained in functional (i.e. vasorelaxation) studies. High affinity [3H]-glibenclamide binding was abolished by prolonged hypoxia combined with metabolic inhibition. The data indicate that the high affinity component of [3H]-glibenclamide binding mediates the block of the KATP channel by the sulphonylureas in rat aorta; hence, it represents the sulphonylurea receptor in this vessel. The pharmacological properties of this binding site resemble those of the binding site for the openers of the KATP channel; present evidence suggests that these two classes of sites are negatively allosterically coupled. Keywords: Glibenclamide binding, sulphonylurea receptor, KATP channel, KATP channel openers, [3H]-P1075, metabolic dependence of binding, rat aorta Full Text The Full Text of this article is available as a PDF (641K). Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society Formats: Summary | PDF (641K) | Citation Share Facebook Twitter Google+ You are here: NCBI > Literature > PubMed Central (PMC) Write to the Help Desk External link. Please review our privacy policy. NLM NIH DHHS USA.gov Copyright | Disclaimer | Privacy | Browsers | Accessibility | Contact National Center for Biotechnology Information, U.S. National Library of Medicine 8600 Rockville Pike, Bethesda MD, 20894 USA