Grapengiesser E, Gylfe E, Hellman B
Department of Medical Cell Biology, Uppsala University, Sweden.
Mol Pharmacol. 1990 Mar;37(3):461-7.
The effects of the insulin-releasing sulfonylurea tolbutamide on the cytoplasmic Ca2+ concentration [( Ca2+]i) in individual pancreatic beta-cells or suspensions of beta-cells were analyzed using the probe fura-2 and dual-wavelength fluorometry. Subsequent additions of 1, 10, and 100 microM tolbutamide induced a graded response, ranging from a single [Ca2+]i peak to a sustained increase. These effects depended on the presence of extracellular Ca2+ and were reversed by the hyperglycemic sulfonamide diazoxide. The responses were diminished in the presence of albumin and varied considerably between different cells. Sometimes tolbutamide triggered slow large amplitude oscillations in [Ca2+]i similar to those induced by glucose. The increase in [Ca2+]i during each tolbutamide-induced oscillation was often more rapid than for glucose-induced oscillations. Oscillations or steady state increases in [Ca2+]i induced by glucose were little influenced by tolbutamide. However, subthreshold concentrations of glucose could reactivate [Ca2+]i response to tolbutamide that had declined. Although in several ways the abilities of glucose and tolbutamide to raise [Ca2+]i were similar, the sulfonylurea lacked a [Ca2+]i-lowering component. The latter effect of glucose was so pronounced that an increase of its concentration from 3 to 20 mM caused temporary lowering of [Ca2+]i to the basal level, even during tolbutamide stimulation. The results indicate that closure of the ATP-sensitive K(+)-channels is important for the large amplitude oscillations of [Ca2+]i the appearance of which reflects the balance between entry of Ca2+ through the voltage-dependent channels and its removal from the cytoplasm.
使用荧光探针fura - 2和双波长荧光测定法分析了胰岛素释放型磺脲类药物甲苯磺丁脲对单个胰腺β细胞或β细胞悬液中细胞质钙离子浓度[Ca2 +]i的影响。随后加入1、10和100微摩尔的甲苯磺丁脲可引起分级反应，范围从单个[Ca2 +]i峰值到持续增加。这些效应依赖于细胞外Ca2 +的存在，并被高血糖磺酰胺类药物二氮嗪逆转。在白蛋白存在的情况下反应减弱，并且在不同细胞之间变化很大。有时甲苯磺丁脲会引发[Ca2 +]i的缓慢大幅度振荡，类似于葡萄糖诱导的振荡。每次甲苯磺丁脲诱导的振荡期间[Ca2 +]i的增加通常比葡萄糖诱导的振荡更快。葡萄糖诱导的[Ca2 +]i振荡或稳态增加受甲苯磺丁脲的影响很小。然而，亚阈值浓度的葡萄糖可以重新激活已经下降的对甲苯磺丁脲的[Ca2 +]i反应。尽管在几个方面葡萄糖和甲苯磺丁脲升高[Ca2 +]i的能力相似，但磺脲类药物缺乏降低[Ca2 +]i的成分。葡萄糖的后一种作用非常明显，以至于其浓度从3毫摩尔增加到20毫摩尔会导致[Ca2 +]i暂时降至基础水平，即使在甲苯磺丁脲刺激期间也是如此。结果表明，ATP敏感性钾通道的关闭对于[Ca2 +]i的大幅度振荡很重要，其出现反映了通过电压依赖性通道进入的Ca2 +与从细胞质中去除的Ca2 +之间的平衡。
