Pharmacological characterization of the sulphonylurea receptor in rat isolated aorta
C Löffler, U Quast - British journal of pharmacology, 1997 - Wiley Online Library
C Löffler, U Quast
British journal of pharmacology, 1997•Wiley Online Library1 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. 2 [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 mg3
wet weight. 3 Other sulphonylureas such as glipizide and glibornuride and the …
triphosphate (ATP)‐sensitive K+ channels (KATP channels), was studied in endothelium‐
denuded rings from rat aorta. 2 [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 mg3
wet weight. 3 Other sulphonylureas such as glipizide and glibornuride and the …
- 1The 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.
- 2[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 mg3 wet weight.
- 3Other 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.
- 4Openers 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.
- 5High affinity [3H]‐glibenclamide binding was abolished by prolonged hypoxia combined with metabolic inhibition.
- 6The 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.
Wiley Online Library