Metabotropic P2 receptor activation regulates oligodendrocyte progenitor migration and development
Metabotropic P2 receptor activation regulates oligodendrocyte progenitor migration and development
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DOI：
10.1002/glia.20160
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发表时间：
2005-04-15
期刊：
影响因子：
6.2
通讯作者：
Visentin, S
中科院分区：
文献类型：
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作者：
Agresti, C;Meomartini, ME;Visentin, S
为了深入了解嘌呤能受体在少突胶质细胞发育中的作用，我们对P2受体在培养的大鼠少突胶质细胞祖细胞中的表达和功能活性进行了表征，并研究了ATP及其分解产物对这种未成熟胶质细胞群迁移和增殖的影响。通过Western blot分析，我们发现少突胶质细胞祖细胞表达多种P2X(P2X(1,2,3,4,7)(1,2,4)（7)()）和P2Y (P2Y)（）受体。通过Fura-2视频成像记录细胞内Ca2+，可以确定P2激动剂的等级效价顺序：ADPbS = ADP =苯甲酰ATP > ATP > ATPgS > UTP, a，b-meATP无效。基于上述发现，基于拮抗剂oxATP和MRS2179的药理抑制作用，以及在全细胞记录中缺乏bmeatp诱导的内向电流，P2X（和P2Y）(1)(被确定为OPs中主要的嗜离子性和代谢性P2受体。作为这些发现的功能相关性，我们发现ATP和代谢激动剂，ADP和P2Y特异性激动剂ADPPS，而不是UTP，诱导少突胶质细胞祖细胞迁移。此外，在纯化培养和小脑组织切片中，ATP和ADP均能抑制血小板源性生长因子诱导的少突胶质细胞祖细胞的增殖。ATP和ADP对细胞迁移和增殖的影响被P2Y(1)(1)（拮抗剂）MRS2179阻断。通过共聚焦激光扫描显微镜，发现P2Y(1)受体定位于发育中的大鼠脑中ng2标记的少突胶质细胞祖细胞中。这些数据表明，ATP和ADP可能通过一种主要涉及P2Y(1)受体激活的机制调节少突胶质细胞祖细胞功能。2005 Wiley-Liss, Inc。
To gain insights into the role of purinergic receptors in oligodendrocyte development, we characterized the expression and functional activity of P2 receptors in cultured rat oligodendrocyte progenitors and investigated the effects of ATP and its breakdown products on the migration and proliferation of this immature glial cell population. Using Western blot analysis, we show that oligodendrocyte progenitors express several P2X (P2X(1,2,3,4,7)(1,2,4)(7)() and P2Y (P2Y)() receptors. Intracellular Ca2+ recording by Fura-2 video imaging allowed to determine the rank potency order of the P2 agonists tested: ADPbS = ADP = Benzoyl ATP > ATP > ATPgS > UTP, a,b-meATP ineffective. Based on the above findings, on pharmacological inhibition by the antagonists oxATP and MRS2179, and on the absence of a,bmeATP-induced inward current in whole-cell recording, P2X) (and P2Y)(1) (were identified as the main ionotropic and metabotropic P2 receptors active in OPs. As a functional correlate of these findings, we show that ATP and, among metabotropic agonists, ADP and the P2Y)(-specific agonist ADPPS, but not UTP, induce oligodendrocyte progenitor migration. Moreover, ATP and ADP inhibited the proliferation of oligodendrocyte progenitors induced by platelet-derived growth factor, both in purified cultures and in cerebellar tissue slices. The effects of ATP and ADP on cell migration and proliferation were prevented by the P2Y)(1)(1) (antagonist MRS2179. By confocal laser scanning microscopy, P2Y)(1) (receptors were localized in NG2-labeled oligodendrocyte progenitors in the developing rat brain. These data indicate that ATP and ADP may regulate oligodendrocyte progenitor functions by a mechanism that involves mainly activation of P2Y)(1) receptors. 2005 Wiley-Liss, Inc.