title: Potentiation of NGF-induced neurite outgrowth in PC12 cells by papaverine: role played by PLC-γ, IP3 receptors.
abstract: 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-γ inhibitor U73122. Furthermore, papaverine's potentiation of NGF-induced neurite outgrowth was also blocked by the co-administration of inositol 1,4,5-trisphosphate (IP(3)) receptor antagonists (xestospongin C and 2-aminoethoxydiphenyl borate (2-APB)) and by reduced expression of IP(3) 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-γ and IP(3) receptors might be involved in the mechanism underlying papaverine's potentiation of neurite outgrowth in PC12 cells.
authors.affiliation: Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Itoh
authors.forename: Tamaki
authors.initials: T
authors.lastname: Ishima
authors.forename: Jan
authors.initials: J
authors.lastname: Kehler
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000502:physiology*; D020932:Nerve Growth Factor / Q000819:agonists*; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D016716:PC12 Cells; D010208:Papaverine / Q000819:agonists / Q000494:pharmacology* / Q000627:therapeutic use; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D051966:Phospholipase C gamma / Q000502:physiology*; D051381:Rats
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D010726:Phosphodiesterase Inhibitors; D020932:Nerve Growth Factor; D010208:Papaverine; D051966:Phospholipase C gamma