title: Na+/Ca2+ exchanger inhibitors inhibit neurite outgrowth in PC12 cells.
abstract: To elucidate the role of Na(+)/Ca(2+) exchanger (NCX) in neurite outgrowth, we investigated the effects of NCX inhibitors on neurite outgrowth in PC12 cells. KB-R7943 and 3',4'-dichlorobenzamil, NCX inhibitors, inhibited the neurite outgrowth caused by nerve growth factor (NGF). NCX inhibitors inhibited the neurite outgrowth caused by dibutylyl cAMP, which rapidly reorganizes the cytoskeleton. KB-R7943 inhibited the neurite outgrowth caused by Y-27632, an inhibitor of Rho kinase (ROCK) that regulates actin. However, NCX inhibitors did not inhibit NGF-induced phosphorylation of extracellular signal-regulated kinase. These results suggest that NCX inhibitor affects downstream of the Rho-ROCK signal transduction pathways in neurite outgrowth.
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Oda
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kume
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Izumi
authors.forename: Kumatoshi
authors.initials: K
authors.lastname: Ishihara
authors.forename: Hachiro
authors.initials: H
authors.lastname: Sugmimoto
authors.forename: Akinori
authors.initials: A
authors.lastname: Akaike
mesh_terms: D000577:Amides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects; D008858:Microscopy, Phase-Contrast; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D009994:Osmolar Concentration; D016716:PC12 Cells; D047428:Protein Kinase Inhibitors / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D000577:Amides; D009419:Nerve Tissue Proteins; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D019831:Sodium-Calcium Exchanger; C041470:3',4'-dichlorobenzamil; C108830:Y 27632; D003994:Bucladesine; D000584:Amiloride; D020932:Nerve Growth Factor; D054460:rho-Associated Kinases; D013890:Thiourea