Suppression of calcium oscillation by tri-n-butyltin chloride in cultured rat hepatocytes.
The effects of tri-n-butyltin chloride (TBT), an environmental pollutant, on cytoplasmic free calcium ion concentration ([Ca2+]i) were investigated in primary cultured rat hepatocytes. A high concentration (4.0 microM) of TBT increased resting levels of [Ca2+]i and then induced cell blebs resulting in cell death within 2 h. The increase in [Ca2+]i, but not the cell death, depended on the presence of extracellular Ca2+, suggesting that the increase in [Ca2+]i is not critical for the cytotoxicity of TBT. A low concentration (0.1 microM) of TBT did not have any toxic effect (decrease in ATP content, decrease in viability, and shape change) on cultured hepatocytes and did not change [Ca2+]i. However, the calcium responses induced by phenylephrine, [Arg8]-vasopressin, and ATP were suppressed in the cells pretreated with 0.1 microM TBT for 30 min. The suppression was not observed in the cells pretreated with 0.1 microM TBT for only 1 min. Pretreatment with 0.1 microM TBT for 30 min had no effect on the inositol 1,4,5-triphosphate content or its increase in response to hormonal stimulation. These results suggest that TBT suppresses hormone-induced calcium responses at nontoxic low concentrations.
Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Tokyo, 158-8501, USA.
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T
Kawanishi
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H
Asoh
T
T
Kato
C
C
Uneyama
K
K
Toyoda
R
R
Teshima
H
H
Ikebuchi
H
H
Ohata
K
K
Momose
T
T
Hayakawa
M
M
Takahashi
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014220:Trialkyltin Compounds / Q000633:toxicity*
D014220:Trialkyltin Compounds; D010656:Phenylephrine; C011559:tributyltin; D015544:Inositol 1,4,5-Trisphosphate