Direct photoaffinity labeling of the putative sulfonylurea receptor in rat β‐cell tumor membranes by [<sup>3</sup>H]glibenclamide

Kramer, Werner; Oekonomopulos, Raymond; Pünter, Jürgen; Summ, Hans-Dieter

doi:10.1016/0014-5793(88)81155-4

Cited by 79 publications

(51 citation statements)

References 17 publications

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“…Previous photo-affinity labeling in β-cells identified three SUR1 proteins in the sizes of 140-kDa, 65-kDa and 33-kDa [35]. [3H] Glibenclamide was predominantly incorporated into the 140-kDa and 33-kDa forms simultaneously but not into the 65-kDa form [36]. Instead, the 65-kDa form was primarily labeled by [3H] glimepiride, a sulfonylurea with different receptor binding kinetics.…”

Section: Discussionmentioning

confidence: 99%

“…Obtaining the complete sequences for SUR2 short forms is expected to allow us to further characterize these channels in recombinant systems. We are aware that we can not completely exclude the involvement of SUR1 short forms [35,36] in underlying I KATPn because several SUR1 splice variants have been reported earlier [38][39][40], and SUR1 signals have been detected by antibodies in heart [41] probably from a short splice variant [40].…”

Section: Discussionmentioning

confidence: 99%

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Cardiac sulfonylurea receptor short form-based channels confer a glibenclamide-insensitive KATP activity

Pu¹,

Ye²,

Kroboth³

et al. 2008

Journal of Molecular and Cellular Cardiology

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The cardiac sarcolemmal ATP-sensitive potassium channel (K ATP ) consists of a Kir6.2 pore and a SUR2 regulatory subunit, which is an ATP-binding cassette (ABC) transporter. K ATP channels have been proposed to play protective roles during ischemic preconditioning. A SUR2 mutant mouse was previously generated by disrupting the first nucleotide-binding domain (NBD1), where a glibenclamide action site was located. In the mutant ventricular myocytes, a non-conventional glibenclamide-insensitive (10 μM), ATP-sensitive current (I KATPn ) was detected in 33% of singlechannel recordings with an average amplitude of 12.3±5.4 pA per patch, an IC 50 to ATP inhibition at 10 μM, and a mean burst duration at 20.6±1.8 ms. Newly designed SUR2-isoform or variantspecific antibodies identified novel SUR2 short forms in the sizes of 28 and 68 kDa in addition to a 150-kDa long form in the sarcolemmal membrane of wild-type (WT) heart. We hypothesized that channels constituted by these short forms that lack NBD1, confer I KATPn . The absence of the long form in the mutant corresponded to loss of the conventional glibenclamide-sensitive K ATP currents (I KATP ) in isolated cardiomyocytes and vascular smooth muscle cells but the SUR2 short forms remained intact. Nested exonic RT-PCR in the mutant indicated that the short forms lacked NBD1 but contained NBD2. The SUR2 short forms co-immunoprecipitated with Kir6.1 or Kir6.2 suggesting that the short forms may function as hemi-transporters reported in other eukaryotic ABC transporter subgroups. Our results indicate that different K ATP compositions may co-exist in cardiac sarcolemmal membrane.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cardiac sulfonylurea receptor short form-based channels confer a glibenclamide-insensitive KATP activity

Pu¹,

Ye²,

Kroboth³

et al. 2008

Journal of Molecular and Cellular Cardiology

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“…However, this does not exclude the possibility that glimepiride and glibenclamide actually bind to different receptor proteins which display different binding characteristics when embedded within the fl-cell membrane. Elucidation of this point will require identification of the binding proteins, e.g., by means of photoaffinity labeling (Kramer et al [30]; see accompanying paper [31]). …”

Section: Discussionmentioning

confidence: 99%

Differential interaction of glimepiride and glibenclamide with the β-cell sulfonylurea receptor I. Binding characteristics

Müller

Hartz

Pünter

et al. 1994

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Glimepiride is a novel sulfonylurea drug for treatment of non-insulin-dependent diabetes mellitus with higher blood sugar lowering efficacy in diabetic patients than glibenclamide raising the question whether this characteristics is in line with different binding of glimepiride and glibenclamide to the 0-cell sulfonylurea receptor. Scatchard plot analysis of [3H]sulfonylurea binding to membranes isolated from rat 0-cell tumors and (RINm5F) insulinoma cells and to RINm5F cells demonstrated that glimepiride has a 2.5-3-fold lower affinity than glibenclamide. This corresponded well to the 8-9-fold higher kof f and 2.5-3-fold higher kon rates of glimepiride compared to glibenclamide as revealed by the dissociation and association kinetics of [3H]sulfonylurea binding and the K d values calculated thereof. In agreement, the concentrations required for half-maximal displacement of [3H]sulfonylurea bound to 0-cell membranes were significantly higher for glimepiride compared to glibenclamide. However, the binding affinity of glimepiride measured by both equilibrium binding and kinetic binding studies upon solubilization of 0-cell tumor membranes and RINm5F cell membranes increased up to the value for glibenclamide. This was primarily based on a drastic decrease of the dissociation rate constant of glimepiride whereas the kinetics of glibenclamide binding remained largely unaffected upon solubilization. These data suggest that the K d value alone is not sufficient for characterization of a suifonylurea drug, since the kinetic binding parameters may also determine its acute blood sugar lowering efficacy.

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“…The most potent of these are the sulphonyureas which are used widely in the management of Type II diabetes mellitus (reviewed by Ashcroft & Ashcroft, 1990;Nelson et al, 1992). These agents control K-ATP channel activity by interacting with a specific receptor site located close to, or within, the channel (Sturgess et al, 1985;Schmid-Antomarchi et al, 1987;Kramer et al, 1988). However, the mechanisms by which occupation of this receptor results in channel closure have not been defined, and the receptor itself has eluded complete characterization.…”

Section: Discussionmentioning

confidence: 99%

Antagonism of the stimulatory effects of efaroxan and glibenclamide in rat pancreatic islets by the imidazoline, RX801080

Brown

Chan

Stillings³

et al. 1993

British J Pharmacology

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1 The imidazoline M2-adrenoceptor antagonist, efaroxan, stimulates insulin secretion from rat isolated islets and antagonizes the ability of diazoxide to inhibit glucose-induced insulin secretion. These effects result from closure of ATP-sensitive potassium channels although the mechanisms involved have not been elucidated. 2 In the present work, we have examined the effects of a close structural analogue of efaroxan, RX801080, in rat isolated islets of Langerhans. RX801080 was found to be ineffective as a stimulator of insulin secretion and did not prevent the inhibition of insulin secretion mediated by diazoxide. 3 RX801080 acted as an antagonist of the actions of several imidazolines (efaroxan, phentolamine and midaglizole) in rat islets. It dose-dependently inhibited the ability of efaroxan to antagonize the effects of diazoxide in islets and also completely inhibited the direct stimulation of insulin secretion mediated by efaroxan. 4 RX801080 also antagonized the effects of the non-imidazoline, ATP-sensitive potassium channel blocker, glibenclamide, in rat islets. It inhibited both the capacity of glibenclamide to stimulate insulin secretion and the ability of glibenclamide to overcome the inhibitory effects of diazoxide in rat islets. 5 Antagonism of glibenclamide responses by RX801080 was not due to inhibition of binding of the sulphonylurea to its receptor on the pancreatic P-cell. 6 The results suggest that imidazoline compounds and sulphonylureas interact with distinct binding sites on islet cells, but that these sites can interact functionally to control islet cell ATP-sensitive potassium channel activity and insulin secretion.

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Direct photoaffinity labeling of the putative sulfonylurea receptor in rat β‐cell tumor membranes by [³H]glibenclamide

Cited by 79 publications

References 17 publications

Cardiac sulfonylurea receptor short form-based channels confer a glibenclamide-insensitive KATP activity

Cardiac sulfonylurea receptor short form-based channels confer a glibenclamide-insensitive KATP activity

Differential interaction of glimepiride and glibenclamide with the β-cell sulfonylurea receptor I. Binding characteristics

Antagonism of the stimulatory effects of efaroxan and glibenclamide in rat pancreatic islets by the imidazoline, RX801080

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Direct photoaffinity labeling of the putative sulfonylurea receptor in rat β‐cell tumor membranes by [3H]glibenclamide

Cited by 79 publications

References 17 publications

Cardiac sulfonylurea receptor short form-based channels confer a glibenclamide-insensitive KATP activity

Cardiac sulfonylurea receptor short form-based channels confer a glibenclamide-insensitive KATP activity

Differential interaction of glimepiride and glibenclamide with the β-cell sulfonylurea receptor I. Binding characteristics

Antagonism of the stimulatory effects of efaroxan and glibenclamide in rat pancreatic islets by the imidazoline, RX801080

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Direct photoaffinity labeling of the putative sulfonylurea receptor in rat β‐cell tumor membranes by [³H]glibenclamide