Expedient synthesis and biochemical properties of an [125I]-labeled analogue of glyburide, a radioligand for ATP-inhibited potassium channels

Robertson, David W.; Schober, Douglas A.; Krushinski, Joseph H.; Mais, Dale E.; Thompson, Dennis C.; Gehlert, Donald R.

doi:10.1021/jm00174a003

Cited by 20 publications

(7 citation statements)

References 3 publications

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“…[ 3 H]glibenclamide binding has been described also in cardiac [Miller et al, 1991;Gopalakrishan et al, 1991], smooth muscle cells [Zini et al, 1991;Kovacs et al, 1991] and in brain microsomes [Robertson et al, 1990]. A K d value of 0.05-10 nM has been reported.…”

Section: Discussionmentioning

confidence: 99%

Characterization of sulfonylurea receptors in isolated human pancreatic islets

Giannaccini¹,

Lupi²,

Trincavelli³

et al. 1998

J. Cell. Biochem.

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Current information on pancreatic islet sulfonylurea receptors has been obtained with laboratory animal pancreatic beta cells or stable beta-cell lines. In the present study, we evaluated the properties of sulfonylurea receptors of human islets of Langherans, prepared by collagenase digestion and density-gradient purification. The binding characteristics of labeled glibenclamide to pancreatic islet membrane preparations were analyzed, displacement studies with several oral hypoglycemic agents were performed, and these latter compounds were tested as for their insulinotropic action on intact human islets. [3H]glibenclamide saturable binding was shown to be linear at < or =0.25 mg/ml protein; it was both temperature and time dependent. Scatchard analysis of the equilibrium binding data at 25 degrees C indicated the presence of a single class of saturable, high-affinity binding sites with a Kd value of 1.0+/-0.07 nM and a Bmax value of 657+/-48 fmol/mg of proteins. The displacement experiments showed the following rank order of potency of the oral hypoglycemic agents we tested: glibenclamide = glimepiride > tolbutamide > chlorpropamide >> metformin. This binding potency order was parallel with the insulinotropic potency of the evaluated compounds.

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Section: Discussionmentioning

confidence: 99%

Characterization of sulfonylurea receptors in isolated human pancreatic islets

Giannaccini¹,

Lupi²,

Trincavelli³

et al. 1998

J. Cell. Biochem.

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“…As seen in Figure 1, all three agents accelerated barrier recovery. In contrast, a single application of two chemically unrelated potassium channel blockers, gilbenclamide (ATP‐dependent) 12 and dequalinium (Ca 2+ ‐dependent), 13 delayed barrier recovery (Fig. 1).…”

Section: Resultsmentioning

confidence: 96%

“…, an ATP-dependent K + channel blocker originally reported to increase intracellular Ca 2+ and stimulate insulin secretion; 12 (v) dequalinium [1,1'-(1,10-decanediyl)bis(4-amino-2-methylquinolinium) chloride: C 30 H 40 Cl 2 N 4 ], another type of K + channel blocker that is Ca 2+ -activated and a selective blocker of the hyperpolation in rat neurones; 13 and (vi) valinomycin, a potassium ionophore. 14…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, if drugs that decrease intracellular K + have opposite effects on barrier homeostasis compared with drugs that increase K + that would provide further support that the changes are specifically due to changes in intracellular K + and not other nonspecific effects. The drugs used in this study include: (i) diazoxide (7‐chloro‐3‐methyl‐2 H ‐1,2,4‐benzothiadiazine 1,1‐dioxide: C 6 H 7 ClN 2 O 2 S), an antihypertensive ATP‐dependent K + channel opener that inhibits insulin secretion in pancreatic beta‐cells; 9 (ii) minoxidil [6‐(1‐piperidinyl)‐2,4‐pyrimidinediamine 3‐oxide: C 9 H 15 N 5 O], another ATP‐dependent K + channel opener originally reported to cause vasodilatation; 10 (iii) 1‐EBIO (1‐ethyl‐2‐benzimidazolinone: C 9 H 10 N 2 O), a different type of K + channel opener – the first epithelial Ca 2+ ‐dependent K + opener; 11 (iv) gilbenclamide {5‐chloro‐ N ‐[2‐[4[[[(cyclohexylamino)carbonyl]amino]sulphonyl]phenyl]ethyl]‐2‐methoxybenzamide: C 23 H 28 ClN 3 O 3 S}, an ATP‐dependent K + channel blocker originally reported to increase intracellular Ca 2+ and stimulate insulin secretion; 12 (v) dequalinium [1,1’‐(1,10‐decanediyl)bis(4‐amino‐2‐methylquinolinium) chloride: C 30 H 40 Cl 2 N 4 ], another type of K + channel blocker that is Ca 2+ ‐activated and a selective blocker of the hyperpolation in rat neurones; 13 and (vi) valinomycin, a potassium ionophore 14 …”

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confidence: 99%

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Potassium channel openers accelerate epidermal barrier recovery

et al. 2007

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“…The binding parameters of [ 3 H]-glibenclamide in rat brain and HIT-T15 b-cell membrane preparations in this study are consistent with those obtained by Zini et al (1991) for rat brain, and French et al (1991) for insulinoma cells. However, in other studies only a single binding site in these tissues has been found (Gaines et al, 1988;Robertson et al, 1990). The variability in [ 3 H]-glibenclamide binding to various tissues has recently been reviewed (Ashcroft & Ashcroft, 1992;Edwards & Weston, 1993).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of BTS 67 582, a novel antidiabetic agent, in normal and diabetic rats

Jones¹,

Dickinson²,

Anthony³

et al. 1997

British J Pharmacology

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1. The effect of BTS 67 582, a novel antidiabetic agent, has been evaluated on plasma glucose and plasma insulin in normal and streptozotocin-induced diabetic rats. 2. BTS 67 582 (3 to 300 mg kg-1, p.o.) caused a dose- and time-dependent reduction in plasma glucose and an increase in plasma insulin in both fasted and glucose-loaded normal rats. The ED50 for the glucose lowering effect of BTS 67 582 in fasted rats was 37.6, 18.4 and 18.5 mg kg-1 at 1, 2 and 4 h after administration respectively. 3. In streptozotocin-induced (50 mg kg-1, i.v.) diabetic rats, BTS 67 582 (37-147 mg kg-1, p.o.) caused significant reductions of plasma glucose following a glucose load, whereas glibenclamide (100 mg kg-1, p.o.) was ineffective. BTS 67 582 significantly increased plasma insulin compared to controls whereas glibenclamide did not. 4. BTS 67 582 did not displace [3H]-glibenclamide from its binding sites in rat brain, guinea-pig ventricle or the HIT-T15 insulinoma beta-cell line. BTS 67 582 does not therefore appear to modulate its action via an effect on the 'sulphonylurea' receptor. 5. In fasted rats, the glucose lowering effect of BTS 67 582 (100 mg kg-1 p.o.) and glibenclamide (1 mg kg-1, p.o.) were antagonized by diazoxide (30 mg kg-1, i.p.). In addition BTS 67 582, like glibenclamide, caused a dose-dependent rightward shift of cromakalim-induced relaxation of noradrenaline precontracted rat aortic strips, suggesting the involvement of KATP channels. 6. In summary, BTS 67 582 produces a blood glucose-lowering effect in normal and streptozotocin-induced diabetic rats associated with increased insulin concentrations. This effect appears to be due to a blockade of ATP-sensitive potassium channel activity via a different binding site to that of glibenclamide.

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Expedient synthesis and biochemical properties of an [125I]-labeled analogue of glyburide, a radioligand for ATP-inhibited potassium channels

Cited by 20 publications

References 3 publications

Characterization of sulfonylurea receptors in isolated human pancreatic islets

Characterization of sulfonylurea receptors in isolated human pancreatic islets

Potassium channel openers accelerate epidermal barrier recovery

Evaluation of BTS 67 582, a novel antidiabetic agent, in normal and diabetic rats

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