title: Suppression of Ca2+ influx through L-type voltage-dependent calcium channels by hydroxyl radical in mouse cerebral cortical neurons.
abstract: In the present study, we investigated the effect of hydroxyl radical (.OH) produced by the Fenton reaction with FeSO(4) to H(2)O(2) on Ca2+ influx by measuring [(45)Ca2+] influx into mouse cerebral cortical neurons in primary culture.OH formed from 3 microM FeSO(4) and 0.01 microM H(2)O(2) significantly reduced 30 mM KCl-induced [(45)Ca2+] influx and this reduction was abolished by .OH scavengers such as N,N'-dimethylthiourea and mannitol. Nifedipine (1 microM), an inhibitor for L-type voltage-dependent Ca2+ channels (VDCCs) showed no additive effect on the reduction of the 30 mM KCl-induced [(45)Ca2+] influx, while the inhibitors for P/Q- and N-type VDCCs showed further suppression of the KCl-induced [(45)Ca2+] influx even in the presence of .OH. Bay k 8644, an activator of L-type VDCCs, dose-dependently stimulated [(45)Ca2+] influx, and this stimulation disappeared in the presence of nifedipine. Similarly, .OH also suppressed significantly [(45)Ca2+] influx induced by Bay k 8644. These inhibitory actions of .OH on the KCl- and Bay k 8644-induced [(45)Ca2+] influx were completely abolished by .OH scavengers. These results indicate that .OH has the activity to suppress Ca2+ influx through L-type VDCCs.
authors.affiliation: Department of Pharmacology, Kawasaki Medical School, Matsushima, Kurashiki 701-0192, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shirotani
authors.forename: M
authors.initials: M
authors.lastname: Katsura
authors.forename: A
authors.initials: A
authors.lastname: Higo
authors.forename: M
authors.initials: M
authors.lastname: Takesue
authors.forename: Y
authors.initials: Y
authors.lastname: Mohri
authors.forename: K
authors.initials: K
authors.lastname: Shuto
authors.forename: C
authors.initials: C
authors.lastname: Tarumi
authors.forename: S
authors.initials: S
authors.lastname: Ohkuma
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000145:classification / Q000187:drug effects; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000494:pharmacology*; D015640:Ion Channel Gating; D017136:Ion Transport / Q000187:drug effects; D007502:Iron Chelating Agents / Q000494:pharmacology; D008353:Mannitol / Q000494:pharmacology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D005296:Ferrous Compounds; D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D009419:Nerve Tissue Proteins; D020867:omega-Agatoxin IVA; D017665:Hydroxyl Radical; C020748:ferrous sulfate; D008353:Mannitol; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038983:1,3-dimethylthiourea; D020866:omega-Conotoxin GVIA; D006861:Hydrogen Peroxide; D013890:Thiourea; D009543:Nifedipine; D003676:Deferoxamine; D002118:Calcium