The mechanisms of nickel uptake by rat primary hepatocyte cultures: role of calcium channels.
The present study was designed to clarify the mechanism of nickel (Ni) uptake in primary cultures of rat hepatocytes. Exposure of the hepatocytes to Ni (2-50 microM; as NiCl2) for up to 6 h was not cytotoxic, as assessed by the tetrazolium-based dye (MTT) assay. Hepatocytes were treated with 10 microM NiCl2 in the absence or presence of calcium (Ca) and magnesium (Mg) (1 mM). Ni uptake was increased by 19% in medium lacking Mg or Ca and was increased by 37% in Ca- and Mg-free medium. The role of Ca channels on Ni uptake by the hepatocytes was investigated. Pretreatment with nicardipine or verapamil (200 microM), potent inhibitors of Ca channels, decreased Ni uptake by 20%. This effect was only observed when the cells were incubated in the absence of Ca. Pretreatment with vasopressin (100 nM), a well-known Ca channel agonist, significantly increased Ni uptake by the hepatocytes (24%). To determine the involvement of carrier-mediated processes on Ni uptake, the effect of temperature was also investigated. At 4 degrees C the Ni uptake was decreased by 20% compared to uptake at 37 degrees C. These results indicate that Ni uptake by the hepatocytes occurs, at least in part, through the Ca channel transport processes. Further study will be required to assess what other mechanisms are involved.
Funakoshi
T
T
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Inoue
T
T
Shimada
H
H
Kojima
S
S
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009532:Nickel / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013696:Temperature
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009532:Nickel; D008274:Magnesium