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Effects of mitiglinide (S 21403) on Kir6.2/SUR1, Kir6.2/SUR2A and Kir6.2/SUR2B types of ATP-sensitive potassium channel.
Reimann F
,
Proks P
,
Ashcroft FM
.
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1. We have investigated the mechanism of action of the novel anti-diabetic agent mitiglinide (S 21403) on Kir6.2/SUR1, Kir6.2/SUR2A and Kir6.2/SUR2B types of ATP-sensitive potassium (K(ATP)) channel. These possess a common pore-forming subunit, Kir6.2, and different regulatory sulphonylurea receptor (SUR) subunits. It is believed that they correspond to native K(ATP) channels in pancreatic beta-cells, heart and non-vascular smooth muscle, respectively. 2. Kir6.2 was coexpressed with SUR1, SUR2A or SUR2B in Xenopus oocytes and macroscopic currents were recorded in giant inside-out membrane patches. Mitiglinide was added to the intracellular membrane surface. 3. Mitiglinide inhibited Kir6.2/SUR currents at two sites: a low-affinity site on Kir6.2 and a high-affinity site on SUR. Low-affinity inhibition was similar for all three types of K(ATP) channel but high-affinity inhibition was greater for Kir6.2/SUR1 currents (IC(50), 4 nM) than for Kir6.2/SUR2A or Kir6.2/SUR2B currents (IC(50), 3 and 5 microM, respectively). 4. Inhibition of Kir6.2/SUR1 currents was only slowly reversible on the time scale of electrophysiological experiments. 5. Kir6.2/SUR1-S1237Y currents, which previously have been shown to lack high affinity tolbutamide inhibition, resembled Kir6.2/SUR2 currents in being unaffected by 100 nM but blocked by 10 microM mitiglinide. 6. Our results show that mitiglinide is a high-affinity drug that shows a 1000 fold greater affinity for the beta-cell type than the cardiac and smooth muscle types of K(ATP) channel, when measured in excised patches.
Aguilar-Bryan,
Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion.
1995, Pubmed
Aguilar-Bryan,
Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion.
1995,
Pubmed
Ashcroft,
Properties and functions of ATP-sensitive K-channels.
1990,
Pubmed
Ashcroft,
Electrophysiology of the pancreatic beta-cell.
1989,
Pubmed
Ashcroft,
Correlating structure and function in ATP-sensitive K+ channels.
1998,
Pubmed
Ashfield,
Identification of the high-affinity tolbutamide site on the SUR1 subunit of the K(ATP) channel.
1999,
Pubmed
,
Xenbase
Barrett-Jolley,
Characterization of K(ATP) channels in intact mammalian skeletal muscle fibres.
1998,
Pubmed
Clement,
Association and stoichiometry of K(ATP) channel subunits.
1997,
Pubmed
Findlay,
Inhibition of ATP-sensitive K+ channels in cardiac muscle by the sulphonylurea drug glibenclamide.
1992,
Pubmed
Gribble,
Properties of cloned ATP-sensitive K+ currents expressed in Xenopus oocytes.
1997,
Pubmed
,
Xenbase
Gribble,
The interaction of nucleotides with the tolbutamide block of cloned ATP-sensitive K+ channel currents expressed in Xenopus oocytes: a reinterpretation.
1997,
Pubmed
,
Xenbase
Gribble,
Tissue specificity of sulfonylureas: studies on cloned cardiac and beta-cell K(ATP) channels.
1998,
Pubmed
,
Xenbase
Gribble,
Differential sensitivity of beta-cell and extrapancreatic K(ATP) channels to gliclazide.
1999,
Pubmed
,
Xenbase
Inagaki,
Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor.
1995,
Pubmed
Inagaki,
A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels.
1996,
Pubmed
Inagaki,
Subunit stoichiometry of the pancreatic beta-cell ATP-sensitive K+ channel.
1997,
Pubmed
Isomoto,
A novel sulfonylurea receptor forms with BIR (Kir6.2) a smooth muscle type ATP-sensitive K+ channel.
1996,
Pubmed
Krause,
Adenosine triphosphate-dependent K currents activated by metabolic inhibition in rat ventricular myocytes differ from those elicited by the channel opener rilmakalim.
1995,
Pubmed
Mogami,
Inhibition of ATP-sensitive K+ channel by a non-sulfonylurea compound KAD-1229 in a pancreatic beta-cell line, MIN 6 cell.
1994,
Pubmed
NULL,
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group.
1998,
Pubmed
Nichols,
Adenosine triphosphate-sensitive potassium channels in the cardiovascular system.
1991,
Pubmed
Ohnota,
Novel rapid- and short-acting hypoglycemic agent, a calcium(2s)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl) propionate (KAD-1229) that acts on the sulfonylurea receptor: comparison of effects between KAD-1229 and gliclazide.
1994,
Pubmed
Quayle,
ATP-sensitive and inwardly rectifying potassium channels in smooth muscle.
1997,
Pubmed
Sakura,
Cloning and functional expression of the cDNA encoding a novel ATP-sensitive potassium channel subunit expressed in pancreatic beta-cells, brain, heart and skeletal muscle.
1995,
Pubmed
Shyng,
Octameric stoichiometry of the KATP channel complex.
1997,
Pubmed
Trube,
Opposite effects of tolbutamide and diazoxide on the ATP-dependent K+ channel in mouse pancreatic beta-cells.
1986,
Pubmed
Tucker,
Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor.
1997,
Pubmed
,
Xenbase
Venkatesh,
Sulfonylureas, ATP-sensitive K+ channels, and cellular K+ loss during hypoxia, ischemia, and metabolic inhibition in mammalian ventricle.
1991,
Pubmed
Zünkler,
Concentration-dependent effects of tolbutamide, meglitinide, glipizide, glibenclamide and diazoxide on ATP-regulated K+ currents in pancreatic B-cells.
1988,
Pubmed
