RRC ID 69222
Author Ishima T, Hashimoto K.
Title Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by ifenprodil: the role of sigma-1 and IP3 receptors.
Journal PLoS One
Abstract 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.
Volume 7(5)
Pages e37989
Published 2012-1-1
DOI 10.1371/journal.pone.0037989
PII PONE-D-12-03613
PMID 22655093
PMC PMC3360021
MeSH Animals Calcium / metabolism Chelating Agents / pharmacology Egtazic Acid / analogs & derivatives Egtazic Acid / pharmacology Inositol 1,4,5-Trisphosphate Receptors / antagonists & inhibitors Inositol 1,4,5-Trisphosphate Receptors / metabolism* Nerve Growth Factor / metabolism* Neurites / drug effects Neurites / metabolism* Neurons / cytology Neurons / drug effects* PC12 Cells Piperidines / pharmacology* Rats Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors Receptors, sigma / metabolism* Vasodilator Agents / pharmacology*
IF 2.74
Human and Animal Cells PC-12(RCB0009)