Neuron degeneration induced by verapamil and attenuated by EGb761.
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.
Zhu
L
L
School of Medicine, Nanjing University, China.
Gao
J
J
Wang
Y
Y
Zhao
X N
XN
Zhang
Z X
ZX
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
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