Colca J R, Kotagal N, Brooks C L, Lacy P E, Landt M, McDaniel M L
J Biol Chem. 1983 Jun 25;258(12):7260-3.
Alloxan was found to inhibit a Ca2+- and calmodulin-dependent protein kinase recently identified in pancreatic islets. This effect of alloxan may be specifically related to the inhibitory action of alloxan on insulin secretion from islets since: 1) in islet-cell subcellular fractions, alloxan at micromolar concentrations irreversibly inhibits the Ca2+- and calmodulin-dependent protein kinase activity; 2) pretreatment of intact islets with alloxan at concentrations that inhibit insulin secretion similarly inhibits the protein kinase activity; and 3) alloxan inhibition of both insulin secretion and protein kinase activity in intact islets can be prevented by D-glucose. This inhibition by alloxan appears to be a direct effect on the enzyme since alloxan treatment of either the islet homogenate or the microsomal fraction enriched in protein kinase activity inhibited the kinase activity with similar concentration dependence. These results suggest that alloxan-induced inhibition of a Ca2+- and calmodulin-dependent protein kinase may represent a critical inhibitory site which mediates alloxan-induced inhibition of insulin secretion.
人们发现，四氧嘧啶能够抑制最近在胰岛中鉴定出的一种钙和钙调蛋白依赖性蛋白激酶。四氧嘧啶的这种作用可能与它对胰岛胰岛素分泌的抑制作用有特定关联，原因如下：1）在胰岛细胞亚细胞组分中，微摩尔浓度的四氧嘧啶可不可逆地抑制钙和钙调蛋白依赖性蛋白激酶的活性；2）用能抑制胰岛素分泌的浓度的四氧嘧啶预处理完整胰岛，同样会抑制蛋白激酶的活性；3）D-葡萄糖能够防止四氧嘧啶对完整胰岛中胰岛素分泌和蛋白激酶活性的抑制作用。四氧嘧啶的这种抑制作用似乎是对该酶的直接作用，因为用四氧嘧啶处理胰岛匀浆或富含蛋白激酶活性的微粒体组分时，对激酶活性的抑制作用具有相似的浓度依赖性。这些结果表明，四氧嘧啶诱导的对钙和钙调蛋白依赖性蛋白激酶的抑制作用可能代表一个关键的抑制位点，该位点介导了四氧嘧啶诱导的胰岛素分泌抑制作用。
