Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by donepezil: Role of sigma-1 receptors and IP3 receptors

2008 ◽  
Vol 32 (7) ◽  
pp. 1656-1659 ◽  
Author(s):  
Tamaki Ishima ◽  
Tomoko Nishimura ◽  
Masaomi Iyo ◽  
Kenji Hashimoto
1986 ◽  
Vol 102 (3) ◽  
pp. 821-829 ◽  
Author(s):  
C Richter-Landsberg ◽  
B Jastorff

Nerve growth factor (NGF)-mediated neurite outgrowth in rat pheochromocytoma PC12 cells has been described to be synergistically potentiated by the simultaneous addition of dibutyryl cAMP. To elucidate further the role of cAMP in NGF-induced neurite outgrowth we have used the adenylate cyclase activator forskolin, cAMP, and a set of chemically modified cAMP analogues, including the adenosine cyclic 3',5'-phosphorothioates (cAMPS) (Rp)-cAMPS and (Sp)-cAMPS. These diastereomers have differential effects on the activation of cAMP-dependent protein kinases, i.e., (Sp)-cAMPS behaves as a cAMP agonist and (Rp)-cAMPS behaves as a cAMP antagonist. Our data show that the establishment of a neuritic network, as observed from PC12 cells treated with NGF alone, could not be induced by either forskolin, cAMP, or cAMP analogues alone. The presence of NGF in combination with forskolin or cAMP or its agonistic analogues potentiated the initiation of neurite outgrowth from PC12 cells. The (Sp)-cAMPS-induced stimulation of NGF-mediated process formation was successfully blocked by the (Rp)-cAMPS diastereomer. On the other hand, NGF-stimulated neurite outgrowth was not inhibited by the presence of the cAMP antagonist (Rp)-cAMPS. We conclude that the morphological differentiation of PC12 cells stimulated by NGF does not require cAMP as a second messenger. The constant increase of intracellular cAMP, caused by either forskolin or cAMP and the analogues, in combination with NGF, not only rapidly stimulated early neurite outgrowth but also exerted a maintaining effect on the neuronal network established by NGF.


PLoS ONE ◽  
2018 ◽  
Vol 13 (12) ◽  
pp. e0209250 ◽  
Author(s):  
Kazuki Terada ◽  
Keisuke Migita ◽  
Yukari Matsushima ◽  
Yumi Sugimoto ◽  
Chiaki Kamei ◽  
...  

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