EFFECTS OF SULFONAMIDES ON A METABOLITE-REGULATED ATPI-SENSITIVE K+ CHANNEL IN RAT PANCREATIC B-CELLS
EFFECTS OF SULFONAMIDES ON A METABOLITE-REGULATED ATPI-SENSITIVE K+ CHANNEL IN RAT PANCREATIC B-CELLS
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DOI：
10.1152/ajpcell.1989.257.6.c1119
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发表时间：
1989-12-01
影响因子：
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通讯作者：
MISLER, S
中科院分区：
文献类型：
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作者：
GILLIS, KD;GEE, WM;MISLER, S
细胞内ATP （ATPi）敏感的K+ [K+(ATP)]通道现在被公认为临床有用的降糖和高血糖磺胺类药物的作用位点。我们进一步研究了这些药物对大鼠胰腺b细胞单个K+通道的作用1)甲磺脲和格列本脲，两种降低细胞附着斑块中K+(ATP)通道活性的降糖磺脲类药物，以类似于葡萄糖的方式影响K+(ATP)通道的动力学。它们缩短了“突发”或开放通道事件簇的持续时间，同时延长了突发之间的间隔。2)高血糖血管扩张剂二氮氧化物增加细胞附着贴片以及暴露于ATP的由内到外切除贴片的K+(ATP)通道的平均活性。它似乎延长了信道爆发，缩短了它们之间的间隔。两种结构相似的利尿剂氢氯噻嗪和速尿具有轻微的高血糖作用，即使达到临床毒性浓度也不会增加K+(ATP)通道活性。3)磺脲类和二氮氧化物均不直接影响正常b细胞中单个延迟整流K+通道或单个钙离子和电压激活K+通道的活性。
Intracellular ATP (ATPi)-sensitive K+ [K+(ATP)] channels are now a recognized site of action of clinically useful hypoglycemic and hyperglycemic sulfonamides. We have further examined the action of these agents on single K+ channels in rat pancreatic B-cells 1) Tolbutamide and glyburide, two hypoglycemic sulfonylureas which decrease K+(ATP) channel activity in the cell-attached patch, affect the kinetics of K+(ATP) channel in a manner similar to glucose. They shorten the duration of the “burst,” or cluster of open channel events, while lengthening the intervals between bursts. 2) The hyperglycemic vasodilator diazoxide increases mean K+(ATP) channel activity in the cell-attached patch as well as in the inside-out excised patch exposed to ATPi. It appears to lengthen channel bursts and shorten the intervals between them. Two structurally similar diuretics, hydrochlorothiazide and furosemide, which have mild hyperglycemic effects, do not increase K+(ATP) channel activity even at clinically toxic concentrations. 3) Neither the sulfonylureas nor diazoxide directly affect the activity of single delayed rectifier K+ channels or single calcium and voltage-activated K+ channels in normal B-cells.