title: Ca2+ channel blockers attenuate beta-amyloid peptide toxicity to cortical neurons in culture.
abstract: Deposit of beta-amyloid protein (A beta) in Alzheimer's disease brain may contribute to the associated neurodegeneration. We have studied the neurotoxicity of A beta in primary cultures of murine cortical neurons, with the aim of identifying pharmacologic ways of attenuating the injury. Exposure of cultures to A beta (25-35 fragment; 3-25 microM) generally triggers slow, concentration-dependent neurodegeneration (over 24-72 h). With submaximal A beta-(25-35) exposure (10 microM), substantial (> 40% within 48 h) degeneration often occurs and is markedly attenuated by the presence of the Ca2+ channel blockers nimodipine (1-20 microM) and Co2+ (100 microM) during the A beta exposure. However, A beta neurotoxicity is not affected by the presence of glutamate receptor antagonists. We suggest that Ca2+ influx through voltage-gated Ca2+ channels may contribute to A beta-induced neuronal injury and that nimodipine and Co2+, by attenuating such influx, are able to attenuate A beta neurotoxicity.
authors.affiliation: Department of Neurology, University of California, Irvine 92717-4290.
authors.forename: J H
authors.initials: JH
authors.lastname: Weiss
authors.forename: C J
authors.initials: CJ
authors.lastname: Pike
authors.forename: C W
authors.initials: CW
authors.lastname: Cotman
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005333:Fetus; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D009553:Nimodipine / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D002121:Calcium Channel Blockers; D009498:Neurotoxins; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D009553:Nimodipine; D016291:Dizocilpine Maleate