An ADP-ribosyltransferase as a potential target for nitric oxide action in hippocampal long-term potentiation.
An ADP-ribosyltransferase as a potential target for nitric oxide action in hippocampal long-term potentiation.
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DOI：
10.1073/pnas.91.25.11958
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发表时间：
1994-12
影响因子：
11.1
通讯作者：
Erin M. Schuman;M. Meffert;H. Schulman;Daniel V. Madison
中科院分区：
文献类型：
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作者：
Erin M. Schuman;M. Meffert;H. Schulman;Daniel V. Madison
最近对海马CA 1区长时程增强（LTP）的研究表明，一氧化氮（NO）可能参与某些形式的LTP，并表明突触后产生的NO是一个候选人，作为一个逆行信使。然而，NO在LTP中的分子靶点仍有待阐明。本研究探讨了两个潜在的NO靶点，可溶性鸟苷酸环化酶或ADP-核糖基转移酶（ADPRT; EC 2.4.2.31）是否在LTP中起作用。cGMP的膜渗透类似物的应用没有产生任何持久的突触强度的改变。此外，cGMP依赖性蛋白激酶抑制剂的应用不能预防LTP。我们发现，海马CA 1区组织具有ADPRT活性，这是显着刺激NO和衰减两种不同的单ADPRT活性抑制剂，叶绿醌和烟酰胺。这些相同抑制剂的细胞外应用可以预防LTP。突触后注射烟酰胺未能减弱LTP，这表明ADPRT活性的关键部位位于非突触后位点。这些结果表明，ADP-核糖基化在LTP中起作用，并与ADPRT可能是NO作用的靶点的想法一致。
Recent studies of long-term potentiation (LTP) in the CA1 region of the hippocampus have demonstrated that nitric oxide (NO) may be involved in some forms of LTP and have suggested that postsynaptically generated NO is a candidate to act as a retrograde messenger. However, the molecular target(s) of NO in LTP remain to be elucidated. The present study examined whether either of two potential NO targets, a soluble guanylyl cyclase or an ADP-ribosyltransferase (ADPRT; EC 2.4.2.31) plays a role in LTP. The application of membrane-permeant analogs of cGMP did not produce any long-lasting alterations in synaptic strength. In addition, application of a cGMP-dependent protein kinase inhibitor did not prevent LTP. We found that the CA1 tissue from hippocampus possesses an ADPRT activity that is dramatically stimulated by NO and attenuated by two different inhibitors of mono-ADPRT activity, phylloquinone and nicotinamide. The extracellular application of these same inhibitors prevented LTP. Postsynaptic injection of nicotinamide failed to attenuate LTP, suggesting that the critical site of ADPRT activity resides at a nonpostsynaptic locus. These results suggest that ADP-ribosylation plays a role in LTP and are consistent with the idea that an ADPRT may be a target of NO action.