The pharmacological properties of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB), a potent inhibitor of glycogen phosphorylase and synthase activity in liver preparations, were characterized in different brain tissue preparations as a prerequisite for using it as a tool to investigate brain glycogen metabolism. Its inhibitory effect on glycogen phosphorylase was studied in homogenates of brain tissue and astrocytes and IC50-values close to 400 nM were found. However, the concentration of DAB needed for inhibition of glycogen shunt activity, i.e. glucose metabolism via glycogen, in intact astrocytes was almost three orders of magnitude higher. Additionally, such complete inhibition required a pre-incubation period, a finding possibly reflecting a limited permeability of the astrocytic membrane. DAB did not affect the accumulation of 2-deoxyglucose-6-phosphate indicating that the transport of DAB is not mediated by the glucose transporter. DAB had no effect on enzymes involving glucose-6-phosphate, i.e. glucose-6-phosphate dehydrogenase, phosphoglucoisomerase and hexokinase. Furthermore, DAB was evaluated in a functional preparation of the isolated mouse optic nerve, in which its presence severely reduced the ability to sustain evoked compound action potentials in the absence of glucose, a condition in which glycogen serves as an important energy substrate. Based on the experimental findings, DAB can be used to evaluate glycogen shunt activity and its functional importance in intact brain tissue and cells at a concentration of 300-1000 muM and a pre-incubation period of 1 h.

中文翻译：

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1，4-dideoxy-1,4-imino-d-arabinitol（DAB）表征脑糖原分流活性的抑制剂。

1，4-二甲氧基-1，4-亚氨基-d-阿拉伯糖醇（DAB）是肝制剂中糖原磷酸化酶和合酶活性的有效抑制剂，其药理特性在不同的脑组织制剂中被表征为将其用作肝素的前提条件。研究脑糖原代谢的工具。在脑组织和星形胶质细胞匀浆中研究了其对糖原磷酸化酶的抑制作用，发现IC50值接近400 nM。然而，在完整的星形胶质细胞中，抑制糖原分流活性（即通过糖原进行的葡萄糖代谢）所需的DAB浓度几乎高出三个数量级。另外，这种完全抑制需要预温育期，这一发现可能反映出星形细胞膜的有限的渗透性。DAB不影响2-脱氧葡萄糖-6-磷酸的积累，表明DAB的转运不受葡萄糖转运蛋白的介导。DAB对涉及6-磷酸葡萄糖的酶（即6-磷酸葡萄糖脱氢酶，磷酸葡萄糖异构酶和己糖激酶）没有影响。此外，在离体的小鼠视神经的功能制剂中对DAB进行了评估，其中DAB的存在严重降低了在没有葡萄糖的情况下维持诱发的复合动作电位的能力，葡萄糖是糖原作为重要能量底物的条件。根据实验结果，DAB可用于评估糖原分流活性及其在完整的脑组织和细胞中的浓度（浓度为300-1000μM，预潜伏期为1 h）。