Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by ifenprodil: the role of sigma-1 and IP3 receptors.

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 signific...

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Autores principales: Tamaki Ishima, Kenji Hashimoto
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Publicado: Public Library of Science (PLoS) 2012
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Acceso en línea:https://doaj.org/article/0801be4b46a842559f5880520344680a
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spelling oai:doaj.org-article:0801be4b46a842559f5880520344680a2021-11-18T07:17:29ZPotentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by ifenprodil: the role of sigma-1 and IP3 receptors.1932-620310.1371/journal.pone.0037989https://doaj.org/article/0801be4b46a842559f5880520344680a2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22655093/?tool=EBIhttps://doaj.org/toc/1932-6203In 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 (IP(3)) receptor antagonists, xestospongin C and 2-aminoethoxydiphenyl borate (2-APB) treatment. Furthermore, BAPTA-AM, a chelator of intracellular Ca(2+), blocked the effects of ifenprodil on NGF-induced neurite outgrowth, indicating the role of intracellular Ca(2+) in the neurite outgrowth. These findings suggest that activation at sigma-1 receptors and subsequent interaction with IP(3) receptors may mediate the pharmacological effects of ifenprodil on neurite outgrowth.Tamaki IshimaKenji HashimotoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e37989 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Tamaki Ishima
Kenji Hashimoto
Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by ifenprodil: the role of sigma-1 and IP3 receptors.
description 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 (IP(3)) receptor antagonists, xestospongin C and 2-aminoethoxydiphenyl borate (2-APB) treatment. Furthermore, BAPTA-AM, a chelator of intracellular Ca(2+), blocked the effects of ifenprodil on NGF-induced neurite outgrowth, indicating the role of intracellular Ca(2+) in the neurite outgrowth. These findings suggest that activation at sigma-1 receptors and subsequent interaction with IP(3) receptors may mediate the pharmacological effects of ifenprodil on neurite outgrowth.
format article
author Tamaki Ishima
Kenji Hashimoto
author_facet Tamaki Ishima
Kenji Hashimoto
author_sort Tamaki Ishima
title Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by ifenprodil: the role of sigma-1 and IP3 receptors.
title_short Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by ifenprodil: the role of sigma-1 and IP3 receptors.
title_full Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by ifenprodil: the role of sigma-1 and IP3 receptors.
title_fullStr Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by ifenprodil: the role of sigma-1 and IP3 receptors.
title_full_unstemmed Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by ifenprodil: the role of sigma-1 and IP3 receptors.
title_sort potentiation of nerve growth factor-induced neurite outgrowth in pc12 cells by ifenprodil: the role of sigma-1 and ip3 receptors.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/0801be4b46a842559f5880520344680a
work_keys_str_mv AT tamakiishima potentiationofnervegrowthfactorinducedneuriteoutgrowthinpc12cellsbyifenprodiltheroleofsigma1andip3receptors
AT kenjihashimoto potentiationofnervegrowthfactorinducedneuriteoutgrowthinpc12cellsbyifenprodiltheroleofsigma1andip3receptors
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