Effect of MgATP on pinacidil‐induced displacement of glibenclamide from the sulphonylurea receptor in a pancreatic β‐cell line and rat cerebral cortex

Schwanstecher, Mathias; Brandt, Christian; Behrends, Sönke; Schaupp, Ursula; Panten, U.

doi:10.1111/j.1476-5381.1992.tb14331.x

Cited by 56 publications

(64 citation statements)

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“…A (Schwanstecher et al, 1992b). In insulin-secreting cells, diazoxide probably does not bind to the site for sulphonylureas (Schwanstecher et al, 1992c). In inside-out patches, there was no evidence for interaction of diazoxide and ATP at a common site (Figure 3) Panten et al, 1990) by binding to the same site occupied by free ATP (EC50 = 4 g.M; Ashcroft & Kakei, 1989; see also Results section) whereas free dADP and GDP are ineffective up to 0.1 or 0.5 mm, respectively (Schwanstecher et al, 1992a).…”

Section: Discussionmentioning

confidence: 99%

Diazoxide‐sensitivity of the adenosine 5′‐triphosphate‐dependent K⁺ channel in mouse pancreatic β‐cells

Schwanstecher¹,

Dickel²,

Ebers³

et al. 1992

British J Pharmacology

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1. In mouse pancreatic P-cells the regulation of the diazoxide-sensitivity of the adenosine 5'-triphosphate-dependent K+ channel (K-ATP-channel) was 5. Diazoxide (50 or 300 jM) prevented the complete channel block induced by saturating tolbutamide concentrations in the presence of Mg2" and ADP (1 mM). 6. In the presence of Mg2", the K-ATP-channel-blocking potency of cytosolic ATP decreased in the order inside-out> outside-out> whole-cell configuration of the patch-clamp technique. 7. It is concluded that the K-ATP-channel is controlled via four separate binding sites for inhibitory nucleotides (e.g. free ATP and ADP), stimulatory nucleotides (MgADP, MgdADP, MgGDP), sulphonylureas and diazoxide. Strong inhibition of the channel openings by sulphonylureas results from occupation of both sites for nucleotides. Diazoxide is only effective when the site for stimulatory nucleotides is occupied.

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Section: Discussionmentioning

confidence: 99%

Diazoxide‐sensitivity of the adenosine 5′‐triphosphate‐dependent K⁺ channel in mouse pancreatic β‐cells

Schwanstecher¹,

Dickel²,

Ebers³

et al. 1992

British J Pharmacology

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“…Data-Data analysis (including calculation of K D values from IC 50 values), and statistics were performed as described (19,20). Results shown as mean Ϯ S.E.…”

Section: Materials and Solutions-[mentioning

confidence: 99%

“…Composition of chimeras was as follows (numbers indicate amino acid boundaries of SUR2B or SUR1 as indicated; see also Binding Experiments-Transfections and membrane preparations were performed as described previously (16,19). Briefly, COS-7 cells cultured in DMEM-HG (10 mM glucose), supplemented with 10% fetal calf serum, were plated at a density of 5 ϫ 10 5 cells per dish (94 mm) and allowed to attach overnight.…”

Section: Materials and Solutions-[mentioning

confidence: 99%

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Identification of the Potassium Channel Opener Site on Sulfonylurea Receptors

Uhde¹,

Toman²,

Gross

et al. 1999

Journal of Biological Chemistry

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123

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“…In addition to two nucleotide-binding domains, SUR possesses binding sites for synthetic K ATP channel modulators. The binding sites for blockers and openers are different, but they are linked via complex allosteric interactions (2,3).…”

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Resveratrol Binds to the Sulfonylurea Receptor (SUR) and Induces Apoptosis in a SUR Subtype-specific Manner

Hambrock

Franz

Hiller

et al. 2007

Journal of Biological Chemistry

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Sulfonylurea receptors (SURs) constitute the regulatory subunits of ATP-sensitive K ؉ channels (K ATP channels). SUR binds nucleotides and synthetic K ATP channel modulators, e.g. the antidiabetic sulfonylurea glibenclamide, which acts as a channel blocker. However, knowledge about naturally occurring ligands of SUR is very limited. In this study, we show that the plant phenolic compound trans-resveratrol can bind to SUR and displace binding of glibenclamide. Electrophysiological measurements revealed that resveratrol is a blocker of pancreatic SUR1/ K IR 6.2 K ATP channels. We further demonstrate that, like glibenclamide, resveratrol induces enhanced apoptosis. This was shown by analyzing different apoptotic parameters (cell detachment, nuclear condensation and fragmentation, and activities of different caspase enzymes). The observed apoptotic effect was specific to cells expressing the SUR1 isoform and was not mediated by the electrical activity of K ATP channels, as it was observed in human embryonic kidney 293 cells expressing SUR1 alone. Enhanced susceptibility to resveratrol was not observed in pancreatic ␤-cells from SUR1 knock-out mice or in cells expressing the isoform SUR2A or SUR2B or the mutant SUR1(M1289T). Resveratrol was much more potent than glibenclamide in inducing SUR1-specific apoptosis. Treatment with etoposide, a classical inducer of apoptosis, did not result in SUR isoform-specific apoptosis. In conclusion, resveratrol is a natural SUR ligand that can induce apoptosis in a SUR isoform-specific manner. Considering the tissue-specific expression patterns of SUR isoforms and the possible effects of SUR mutations on susceptibility to apoptosis, these observations could be important for diabetes and/or cancer research.Sulfonylurea receptors (SURs) 2 are members of the ATPbinding cassette protein family (subfamily C). SURs are known to be the important regulatory subunits of ATP-sensitive K ϩ channels (K ATP channels). These channels are heteromeric complexes composed of four SUR subunits that surround a central pore formed by four subunits from the K IR 6.x family. K ATP channels found in various tissues exhibit distinct physiological and pharmacological properties because of the combination of different subunit isoforms (reviewed in Ref. 1). In addition to two nucleotide-binding domains, SUR possesses binding sites for synthetic K ATP channel modulators. The binding sites for blockers and openers are different, but they are linked via complex allosteric interactions (2, 3).Because of their nucleotide sensitivity, K ATP channels couple the energy metabolism of a cell to the membrane potential. This is important in the pancreatic ␤-cell, in which closure of K ATP channels triggers insulin secretion via membrane depolarization in response to changes in blood glucose levels (4 -6). K ATP channel-blocking drugs such as the sulfonylureas and the glinides can promote insulin secretion and are used in the treatment of diabetes type 2. Insulin secretion is also modulated and amplified by other pathways...

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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

Cited by 56 publications

References 47 publications

Diazoxide‐sensitivity of the adenosine 5′‐triphosphate‐dependent K⁺ channel in mouse pancreatic β‐cells

Diazoxide‐sensitivity of the adenosine 5′‐triphosphate‐dependent K⁺ channel in mouse pancreatic β‐cells

Identification of the Potassium Channel Opener Site on Sulfonylurea Receptors

Resveratrol Binds to the Sulfonylurea Receptor (SUR) and Induces Apoptosis in a SUR Subtype-specific Manner

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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

Cited by 56 publications

References 47 publications

Diazoxide‐sensitivity of the adenosine 5′‐triphosphate‐dependent K+ channel in mouse pancreatic β‐cells

Diazoxide‐sensitivity of the adenosine 5′‐triphosphate‐dependent K+ channel in mouse pancreatic β‐cells

Identification of the Potassium Channel Opener Site on Sulfonylurea Receptors

Resveratrol Binds to the Sulfonylurea Receptor (SUR) and Induces Apoptosis in a SUR Subtype-specific Manner

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Diazoxide‐sensitivity of the adenosine 5′‐triphosphate‐dependent K⁺ channel in mouse pancreatic β‐cells

Diazoxide‐sensitivity of the adenosine 5′‐triphosphate‐dependent K⁺ channel in mouse pancreatic β‐cells