Distribution of ectonucleotidases in the rodent brain revisited
Distribution of ectonucleotidases in the rodent brain revisited
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DOI：
10.1007/s00441-008-0681-x
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发表时间：
2008-11-01
影响因子：
3.6
通讯作者：
Zimmermann, Herbert
中科院分区：
文献类型：
--
作者：
Langer, David;Hammer, Klaus;Zimmermann, Herbert
核苷酸包括神经系统中的主要类别的信号分子。它们可以从神经细胞、神经胶质细胞和血管细胞释放，在那里它们通过亲离子型（P2 X）或亲代谢型（P2 Y）受体发挥其功能。通过细胞外核苷酸以及腺苷的信号传导由位于细胞表面的酶（外核苷酸酶）控制和调节，所述酶将核苷酸水解为相应的核苷。核苷酸配体的细胞外水解涉及相当多的具有不同催化性质的酶，其差异地影响核苷酸信号传导途径。因此，重要的是研究哪种类型的外核苷酸酶有助于在不同的细胞和生理环境中控制核苷酸信号传导。通过使用经典的酶组织化学方法，并采用各种底物，抑制剂和敲除动物，我们提供了，第一次，反映四个外核苷酸酶家族的催化活性的总体分布的比较分析：外-5 '-核苷酸酶，碱性磷酸酶，外核苷三磷酸二磷酸水解酶（E-NTPDases），和外核苷酸焦磷酸酶/磷酸二酯酶（E-NPPs）。我们的角度来看，早期的文献，并提供新的证据，在小鼠脑组织的非特异性碱性磷酸酶，E-NPPs和E-NTPDases的实质定位。此外，我们指定的位置内的脑血管外核苷酸酶。最值得注意的是，脑血管不表达外-5 '-核苷酸酶。个别酶的优势在大脑不同部位之间有很大差异。所有类型的外核苷酸酶的贡献，因此需要考虑在脑中的嘌呤能信号的生理和药理学研究。
Nucleotides comprise a major class of signaling molecules in the nervous system. They can be released from nerve cells, glial cells, and vascular cells where they exert their function via ionotropic (P2X) or metabotropic (P2Y) receptors. Signaling via extracellular nucleotides and also adenosine is controlled and modulated by cell-surface-located enzymes (ectonucleotidases) that hydrolyze the nucleotide to the respective nucleoside. Extracellular hydrolysis of nucleotide ligands involves a considerable number of enzymes with differing catalytic properties differentially affecting the nucleotide signaling pathway. It is therefore important to investigate which type of ectonucleotidase(s) contributes to the control of nucleotide signaling in distinct cellular and physiological settings. By using a classical enzyme histochemical approach and employing various substrates, inhibitors, and knockout animals, we provide, for the first time, a comparative analysis of the overall distribution of catalytic activities reflecting four ectonucleotidase families: ecto-5'-nucleotidase, alkaline phosphatases, ectonucleoside triphosphate diphosphohydrolases (E-NTPDases), and ectonucleotide pyrophyphatases/phosphodiesterases (E-NPPs). We place into perspective the earlier literature and provide novel evidence for a parenchymal localization of tissue non-specific alkaline phosphatase, E-NPPs, and E-NTPDases in the mouse brain. In addition, we specify the location of ectonucleotidases within the brain vasculature. Most notably, brain vessels do not express ecto-5'-nucleotidase. The preponderance of individual enzymes differs considerably between brain locations. The contribution of all types of ectonucleotidases thus needs to be considered in physiological and pharmacological studies of purinergic signaling in the brain.