title: Neuron degeneration induced by verapamil and attenuated by EGb761.
abstract: Calcium channel blockers are used as neuroprotective agents, as glutamate antagonists. However, it has been found that calcium channel blockers may compromise neuronal survival after long-term exposure. To explore the mechanisms of the toxicity of calcium channel blockers on neurons, we studied the morphological characteristics and biochemical changes of cultured cortical neurons treated with verapamil, a calcium channel blocker. We now report that cerebral cortical cultures exposed to verapamil for 48 h undergo neuronal degeneration in both concentration-dependent and time-dependent fashion, possibly partially through the activation of apoptosis. On the other hand, it was found that Ginkgo biloba extract (EGb761) attenuated verapamil-induced neuronal injury, suggesting the possibility of using verapamil combined with EGb761 clinically. Furthermore, both B-50 immunoactivity (BIA) and the concentration of intracellular calcium in single neurons ([Ca2+]i) decreased after a 48-h exposure to verapamil, suggesting that the mechanisms of verapamil-induced degeneration may be associated with the disruption of intracellular calcium homeostasis and the inhibition of normal axonal elongation.
authors.affiliation: School of Medicine, Nanjing University, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhu
authors.forename: J
authors.initials: J
authors.lastname: Gao
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: X N
authors.initials: XN
authors.lastname: Zhao
authors.forename: Z X
authors.initials: ZX
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001369:Axons / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000648:ultrastructure*; D004224:Diterpenes; D005419:Flavonoids / Q000494:pharmacology*; D019922:GAP-43 Protein / Q000032:analysis; D020441:Ginkgo biloba; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology; D051379:Mice; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure*; D010936:Plant Extracts; D013997:Time Factors; D014700:Verapamil / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000096983:Ginkgo Extract
chemical_list: D002121:Calcium Channel Blockers; D004224:Diterpenes; D005419:Flavonoids; D019922:GAP-43 Protein; D046934:Ginkgolides; D007783:Lactones; D010936:Plant Extracts; D014700:Verapamil; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C045856:ginkgolide B