Potentiation of NGF-induced neurite outgrowth in PC12 cells by papaverine: Role played by PLC-γ, IP3 receptors
Potentiation of NGF-induced neurite outgrowth in PC12 cells by papaverine: Role played by PLC-γ, IP3 receptors
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DOI：
10.1016/j.brainres.2010.12.075
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发表时间：
2011-03-04
期刊：
影响因子：
2.9
通讯作者：
Hashimoto, Kenji
中科院分区：
文献类型：
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作者：
Itoh, Kanako;Ishima, Tamaki;Hashimoto, Kenji
罂粟碱是一种磷酸二酯酶(PDE)10A的抑制剂，因其在治疗精神分裂症等神经精神疾病方面的潜力而受到关注。然而，罂粟碱潜在的神经保护/神经营养作用的确切机制仍不清楚。因此，我们研究了罂粟碱对神经生长因子(NGF)诱导的PC12细胞突起生长的影响。罂粟碱以浓度依赖的方式增强NGF诱导的PC12细胞突起生长。相反，选择性PDE10A抑制剂MP-10对NGF诱导的神经突起生长没有影响。罂粟碱对NGF诱导的神经突起生长的促进作用可被PLC-γ抑制剂U73122阻断。此外，罂粟碱对NGF诱导的神经突起生长的增强作用也可被肌醇1，4，5-三磷酸(IP3)受体拮抗剂(xestospongin C和2-氨基乙氧基二苯硼酸酯(2-APB))联合应用以及通过siRNA降低IP3受体基因(即ITPR1和itpr3)的表达而被阻断。结果提示，罂粟碱可促进NGF诱导的PC12细胞突起生长，其机制可能与激活PLC-γ和IP3受体有关。(C)2010爱思唯尔B.V.保留所有权利。
Papaverine, an inhibitor of phosphodiesterase (PDE) 10A, is gaining attention for its potential in the treatment of neuropsychiatric diseases such as schizophrenia. However, the precise mechanisms underlying the putative neuroprotective/neurotrophic actions of papaverine remain unclear. Thus, we investigated the effects of papaverine on nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. Papaverine potentiated NGF-induced neurite outgrowth in PC12 cells in a concentration-dependent manner. In contrast, the selective PDE10A inhibitor MP-10 had no effect on NGF-induced neurite outgrowth. The potentiation of NGF-induced neurite outgrowth by papaverine was blocked by the PLC-gamma inhibitor U73122. Furthermore, papaverine's potentiation of NGF-induced neurite outgrowth was also blocked by the co-administration of inositol 1,4,5-trisphosphate (IP3) receptor antagonists (xestospongin C and 2-aminoethoxydiphenyl borate (2-APB)) and by reduced expression of IP3 receptor gene (i.e., itpr1 and itpr3) by siRNA. Our findings suggest that papaverine could potentiate NGF-induced neurite outgrowth, and that activation of PLC-gamma and IP3 receptors might be involved in the mechanism underlying papaverine's potentiation of neurite outgrowth in PC12 cells. (C) 2010 Elsevier B.V. All rights reserved.