Glycogenolysis and Purinergic Signaling
Glycogenolysis and Purinergic Signaling
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DOI：
10.1007/978-3-319-08894-5_3
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发表时间：
2014-01-01
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影响因子：
--
通讯作者：
Peng, Liang
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文献类型：
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作者：
Hertz, Leif;Xu, Junnan;Peng, Liang
三磷酸腺苷和谷氨酸一方面是大脑中必不可少的代谢物，另一方面也起着传递信号的作用。然而，最大的不同之处在于，产生递质谷氨酸的通量与大脑中葡萄糖代谢的速率相当，而产生递质ATP的通量比ATP和ADP之间的代谢周转率小一个数量级。此外，谷氨酸仅在星形胶质细胞中产生，而递质三磷酸腺苷则在神经元和星形胶质细胞中产生。本章仅涉及三磷酸腺苷及其在星形胶质细胞中的形成和释放，并重点讨论与糖原分解的潜在联系，糖原分解是谷氨酸合成所必需的。糖原分解依赖于细胞内游离钙浓度的增加(钙](I))。CAMP可以进一步刺激它，但与人们普遍认为的相反，cAMP本身不能诱导糖原分解。星形胶质细胞从积累的腺苷中产生ATP，这一过程似乎不需要糖原分解。产生的一小部分ATP被用作递质，其合成需要主要在细胞内的核苷转运蛋白ENT3的存在。许多递质以及细胞外K+浓度高到足以打开电压敏感的L钙通道，导致星形胶质细胞释放递质三磷酸腺苷。腺苷和三磷酸腺苷通过作用于几种不同的嘌呤能受体来诱导三磷酸腺苷的释放。递质或K+浓度升高引起的释放可被糖原分解抑制剂DAB消除。
Both ATP and glutamate are on one hand essential metabolites in brain and on the other serve a signaling function as transmitters. However, there is the major difference that the flux in the pathway producing transmitter glutamate is comparable to the rate of glucose metabolism in brain, whereas that producing transmitter ATP is orders of magnitude smaller than the metabolic turnover between ATP and ADP. Moreover, de novo glutamate production occurs exclusively in astrocytes, whereas transmitter ATP is produced both in neurons and astrocytes. This chapter deals only with ATP and exclusively with its formation and release in astrocytes, and it focuses on potential associations with glycogenolysis, which is known to be indispensable for the synthesis of glutamate. Glycogenolysis is dependent upon an increase in free intracellular Ca2+ concentration (Ca2+](i)). It can be further stimulated by cAMP, but in contrast to widespread beliefs, cAMP can on its own not induce glycogenolysis. Astrocytes generate ATP from accumulated adenosine, and this process does not seem to require glycogenolysis. A minor amount of the generated ATP is utilized as a transmitter, and its synthesis requires the presence of the mainly intracellular nucleoside transporter ENT3. Many transmitters as well as extracellular K+ concentrations high enough to open the voltage-sensitive L-channels for Ca2+ cause a release of transmitter ATP from astrocytes. Adenosine and ATP induce release of ATP by action at several different purinergic receptors. The release evoked by transmitters or elevated K+ concentrations is abolished by DAB, an inhibitor of glycogenolysis.