Braun Norbert, Sévigny Jean, Robson Simon C, Hammer Klaus, Hanani Menachem, Zimmermann Herbert
Biozentrum der J.W. Goethe-Universitaet, AK Neurochemie, Zoologisches Institut, Marie-Curie-Strasse 9, D-60439 Frankfurt am Main, Germany.
Glia. 2004 Jan 15;45(2):124-32. doi: 10.1002/glia.10309.
Cellular signaling via extracellular nucleotides appears to play a major role in the functioning of the peripheral nervous system. Information regarding the functional characterization of nucleotide P2 receptors or their expression pattern has been accumulating rapidly; however, very little is known regarding the distribution of ecto-nucleotidases in the periphery. The extracellular level of nucleotides is controlled by ecto-nucleotidases, whereby the three membrane-bound members of the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) family are of special functional importance. Using enzyme histochemistry and immunostaining, we demonstrate that NTPDase2 is associated with nonmyelinating Schwann cells of the rat sciatic nerve, whereas NTPDase1 is restricted to blood vessel walls. NTPDase2 immunoreactivity was detected from embryonic day E18 onward, suggesting that immature Schwann cells express the enzyme. With the onset of myelination, NTPDase2 immunoreactivity remained associated solely with nonmyelinating Schwann cells. NTPDase2 was absent from perisynaptic Schwann cells but was associated with fibroblasts covering the endplate at some distance. In addition, NTPDase2 immunoreactivity was associated with the satellite glial cells in dorsal root ganglia and sympathetic ganglia, and with the enteric glia surrounding the cell bodies of ganglionic neurons of the myenteric and the submucous plexus. In contrast to NTPDase1, NTPDase2 preferentially hydrolyzes nucleoside triphosphates over nucleoside diphosphates and thus can act either in inactivating or in producing P2 receptor ligands. Our results suggest that NTPDase2 plays an important role in the control of nucleotide-mediated activation of peripheral neurons or glia and in the dialogue between these two cell types.
通过细胞外核苷酸进行的细胞信号传导似乎在周围神经系统的功能中发挥着主要作用。关于核苷酸P2受体的功能特性或其表达模式的信息一直在迅速积累；然而，关于外周核酸外切酶的分布却知之甚少。核苷酸的细胞外水平由核酸外切酶控制，其中胞外核苷三磷酸二磷酸水解酶（E-NTPDase）家族的三个膜结合成员具有特殊的功能重要性。利用酶组织化学和免疫染色，我们证明NTPDase2与大鼠坐骨神经的无髓施万细胞相关，而NTPDase1仅限于血管壁。从胚胎第18天开始检测到NTPDase2免疫反应性，这表明未成熟的施万细胞表达该酶。随着髓鞘形成的开始，NTPDase2免疫反应性仅与无髓施万细胞相关。突触周围施万细胞中不存在NTPDase2，但与覆盖终板一定距离的成纤维细胞相关。此外，NTPDase2免疫反应性与背根神经节和交感神经节中的卫星神经胶质细胞以及肌间神经丛和黏膜下神经丛的神经节神经元胞体周围的肠神经胶质细胞相关。与NTPDase1不同，NTPDase2优先水解核苷三磷酸而不是核苷二磷酸，因此可以在使P2受体配体失活或产生P2受体配体方面发挥作用。我们的结果表明，NTPDase2在控制核苷酸介导的外周神经元或神经胶质细胞激活以及这两种细胞类型之间的对话中起重要作用。
