Effect of Tolbutamide and Glyburide on cAMP-Dependent Protein Kinase Activity in Rat Liver Cytosol
Effect of Tolbutamide and Glyburide on cAMP-Dependent Protein Kinase Activity in Rat Liver Cytosol
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甲苯磺丁脲和格列本脲对大鼠肝细胞溶胶中 cAMP 依赖性蛋白激酶活性的影响
作者：
S. Okuno;M. Inaba;Y. Nishizawà;A. Inoue;H. Morii
本文观察了磺脲类、甲苯磺丁胺和格列本脲对大鼠肝细胞浆中腺苷环化酶和cAMP依赖的蛋白激酶(A-K)的影响。甲苯丁脲和格列本脲均以剂量依赖方式抑制A-激酶活性。甲苯磺丁脲和格列本脲分别在10 mM和0.2 mM时达到最大抑制，说明格列本脲的抑制作用是甲苯丁脲的50倍。甲苯丁脲和格列本脲均不影响[~3H]cAMP与蛋白激酶的结合，但均抑制A-激酶催化单位的活性。Lineweaver-Burk双互易图显示，这些药物对蛋白质底物组蛋白以及磷酸供体底物ATP的抑制作用是非竞争性的。因此，甲苯丁脲和格列本脲抑制大鼠肝细胞浆中A-激酶的活性，提示磺脲类药物可能通过抑制A-激酶而影响肝脏的碳水化合物代谢。事实上，这两种药物对A-激酶活性的相对效力与它们所报道的抗糖尿病作用是一致的。
The effect of sulfonylureas tolbutamide and glyburide on adenylate cyclase– and cAMP-dependent protein kinase (A-kinase) was examined in rat liver cytosol. Both tolbutamide and glyburide inhibited the A-kinase activity in a dose-dependent manner. Half-maximal inhibition was obtained at 10 mM with tolbutamide and at 0.2 mM with glyburide, indicating that glyburide was 50-fold as potent as tolbutamide. Neither tolbutamide nor glyburide affected [3H]cAMP binding to the protein kinase, but both inhibited the activity of catalytic units of the A-kinase. Lineweaver-Burk double-reciprocal plots revealed that the inhibitory effects of these drugs were noncompetitive with respect to the protein substrate histone, as well as to the phosphate-donor substrate ATP. Thus, tolbutamide and glyburide inhibited the A-kinase activity in rat liver cytosol, and it was suggested that, through the inhibition of A-kinase, the sulfonylureas would affect the carbohydrate metabolism in the liver. In fact, the relative potencies of these two drugs on A-kinase activity corresponded well with those of their reported antidiabetic effects.
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DOI：
10.1073/pnas.77.10.5861
发表时间：
1980
影响因子：
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作者：
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通讯作者：
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DOI：
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发表时间：
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期刊：
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影响因子：
--
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DOI：
10.1016/0006-291x(82)91359-6
发表时间：
1982
影响因子：
3.1
作者：
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DOI：
--
发表时间：
1982
期刊：
The Journal of biological chemistry
影响因子：
--
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通讯作者：
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DOI：
--
发表时间：
1982
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
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通讯作者：
Pilkis,SJ