Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by ifenprodil: the role of sigma-1 and IP3 receptors.
Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by ifenprodil: the role of sigma-1 and IP3 receptors.
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DOI：
10.1371/journal.pone.0037989
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Hashimoto K
中科院分区：
文献类型：
--
作者：
Ishima T;Hashimoto K
除α1肾上腺素能受体和N-甲基-D-天冬氨酸（NMDA）受体拮抗剂外，艾芬地尔还与σ受体亚型1和2结合。在这项研究中，我们研究了艾芬地尔对神经生长因子（NGF）诱导的PC 12细胞突起生长的影响。艾芬地尔以浓度依赖性方式显著增强NGF诱导的神经突生长。相反，α1肾上腺素能受体拮抗剂哌唑嗪和NMDA受体NR 2B拮抗剂Ro 25-6981不改变NGF诱导的神经突生长。通过共同施用选择性σ-1受体拮抗剂NE-100而不是σ-2受体拮抗剂SM-21，显著拮抗由艾芬地尔介导的NGF诱导的神经突生长的增强。同样，艾芬地尔增强神经生长因子诱导的神经突起生长再次显着减少肌醇1，4，5-三磷酸（IP 3）受体拮抗剂，xestospongin C和2-氨基乙氧基二苯基硼酸酯（2-APB）治疗。此外，BAPTA-AM，胞内Ca 2+的螯合剂，阻断了ifenprodil对NGF诱导的神经突起生长的影响，表明胞内Ca 2+在神经突起生长中的作用。这些发现表明，激活sigma-1受体和随后与IP 3受体的相互作用可能介导艾芬地尔对神经突生长的药理作用。
In addition to both the α1 adrenergic receptor and N-methyl-D-aspartate (NMDA) receptor antagonists, ifenprodil binds to the sigma receptor subtypes 1 and 2. In this study, we examined the effects of ifenprodil on nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. Ifenprodil significantly potentiated NGF-induced neurite outgrowth, in a concentration-dependent manner. In contrast, the α1 adrenergic receptor antagonist, prazosin and the NMDA receptor NR2B antagonist, Ro 25-6981 did not alter NGF-induced neurite outgrowth. Potentiation of NGF-induced neurite outgrowth mediated by ifenprodil was significantly antagonized by co-administration of the selective sigma-1 receptor antagonist, NE-100, but not the sigma-2 receptor antagonist, SM-21. Similarly, ifenprodil enhanced NGF-induced neurite outgrowth was again significantly reduced by the inositol 1,4,5-triphosphate (IP3) receptor antagonists, xestospongin C and 2-aminoethoxydiphenyl borate (2-APB) treatment. Furthermore, BAPTA-AM, a chelator of intracellular Ca2+, blocked the effects of ifenprodil on NGF-induced neurite outgrowth, indicating the role of intracellular Ca2+ in the neurite outgrowth. These findings suggest that activation at sigma-1 receptors and subsequent interaction with IP3 receptors may mediate the pharmacological effects of ifenprodil on neurite outgrowth.
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DOI：
10.1016/0922-4106(94)90211-9
发表时间：
1994-01-01
期刊：
EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION
影响因子：
--
作者：
HASHIMOTO, K;MANTIONE, CR;LONDON, ED
通讯作者：
LONDON, ED
靶向配体的伴侣伴侣Sigma-1受体在神经精神疾病的治疗中。
影响因子：
5.8
作者：
Hayashi T;Tsai SY;Mori T;Fujimoto M;Su TP
通讯作者：
Su TP
影响因子：
13.5
作者：
Maurice T;Su TP
通讯作者：
Su TP
影响因子：
3
作者：
Hashimoto, Kenji
通讯作者：
Hashimoto, Kenji
影响因子：
2.9
作者：
Itoh, Kanako;Ishima, Tamaki;Hashimoto, Kenji
通讯作者：
Hashimoto, Kenji