Extracellular heavy-metal ions stimulate Ca2+ mobilization in hepatocytes

Populations of hepatocytes in primary culture were loaded with fura 2 and the effects of extracellular heavy-metal ions were examined under conditions that allowed changes in fura 2 fluorescence (R340/360, the ratio of fluorescence recorded at 340 and 360 nm) to be directly attributed to changes in...

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Bibliographic Details
Published in:Biochemical journal 1999-05, Vol.339 ( Pt 3) (Pt 3), p.555-561
Main Authors: McNulty, T J, Taylor, C W
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - pharmacology
Animals
Arginine Vasopressin - pharmacology
Cadmium Chloride - pharmacology
Calcium - metabolism
Calcium - pharmacology
Cell Line
Cells, Cultured
Chlorides - pharmacology
Cobalt - pharmacology
Copper - pharmacology
Ethylenediamines - pharmacology
Fluorescence
Fura-2 - metabolism
Hydrogen-Ion Concentration
Lanthanum - pharmacology
Liver - cytology
Liver - drug effects
Liver - metabolism
Magnesium - metabolism
Male
Manganese Compounds - pharmacology
Metals, Heavy - metabolism
Metals, Heavy - pharmacology
Nickel - metabolism
Nickel - pharmacology
Rats
Rats, Wistar
Space life sciences
Zinc Compounds - pharmacology
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Summary:Populations of hepatocytes in primary culture were loaded with fura 2 and the effects of extracellular heavy-metal ions were examined under conditions that allowed changes in fura 2 fluorescence (R340/360, the ratio of fluorescence recorded at 340 and 360 nm) to be directly attributed to changes in cytosolic free [Ca2+] ([Ca2+]i). In Ca2+-free media, Ni2+ [EC50 (concentration causing 50% stimulation) approximately 24+/-9 microM] caused reversible increases in [Ca2+]i that resulted from mobilization of the same intracellular Ca2+ stores as were released by [Arg8]vasopressin. The effects of Ni2+ were not mimicked by increasing the extracellular [Mg2+], by addition of MnCl2, CoCl2 or CdCl2 or by decreasing the extracellular pH from 7.3 to 6.0; nor were they observed in cultures of smooth muscle, endothelial cells or pituitary cells. CuCl2 (80 microM), ZnCl2 (80 microM) and LaCl3 (5 mM) mimicked the ability of Ni2+ to evoke Ca2+ mobilization. The response to La3+ was sustained even in the absence of extracellular Ca2+, probably because La3+ also inhibited Ca2+ extrusion. Although Ni2+ entered hepatocytes, from the extent to which it quenched fura 2 fluorescence the free cytosolic [Ni2+] ([Ni2+]i) was estimated to be
ISSN:0264-6021
1470-8728
DOI:10.1042/0264-6021:3390555