title: Tributyltin-induced Ca(2+) mobilization via L-type voltage-dependent Ca(2+) channels in PC12 cells.
abstract: The effects of tributyltin (TBT) on cytosolic Ca(2+) concentration ([Ca(2+)](c)) and cell viability were investigated in nerve growth factor-differentiated PC12 cells. TBT concentration dependently increased [Ca(2+)](c) with an EC(50) value of 0.07μM. This effect was markedly reduced by removal of the extracellular Ca(2+) or membrane depolarization with a high K(+) medium, but unaffected by thapsigargin causing depletion of intracellular Ca(2+) stores. The L-type voltage-dependent Ca(2+) channel (VDCC) blocker nicardipine blocked the effect of TBT, but the N-type VDCC blocker ω-conotoxin did not. TBT decreased the number of viable cells with an EC(50) value of 0.09μM. The TBT-induced cell death was prevented by nicardipine or by chelating the cytosolic Ca(2+) with BAPTA-AM, but not by ω-conotoxin. The results show that TBT causes an increase in [Ca(2+)](c) via activating L-type VDCCs, and support the idea that the organotin-induced cell death arises through Ca(2+) mobilization via L-type VDCCs.
authors.affiliation: Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Applied Biological Science, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; Department of Pathogenetic Veterinary Science, United Graduate School of Veterinary Science, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Unno
authors.forename: Ryoko
authors.initials: R
authors.lastname: Iida
authors.forename: Masashi
authors.initials: M
authors.lastname: Okawa
authors.forename: Hayato
authors.initials: H
authors.lastname: Matsuyama
authors.forename: Muhammad Mubarak
authors.initials: MM
authors.lastname: Hossain
authors.forename: Haruo
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Seiichi
authors.initials: S
authors.lastname: Komori