thapsigargin and quinone

Exposure of murine peritoneal macrophages to very low concentrations of 1,4-benzoquinone (BQ) induced immediate increases in intracellular Ca2+ concentrations ([Ca2+]i). Increases in [Ca2+]i were induced by concentrations as low as 5 nM and the response was dose dependent and linear up to 1 microM. The sources of Ca2+ were from both internal inositol triphosphate (IP3)-sensitive and -insensitive sites and from the external medium. BQ did not induce IP3 formation and did not affect binding to its receptors. 1, 4-Hydroquinone had no effect on [Ca2+]i. Catechol did elicit some increases in [Ca2+]i, but did so only at much higher concentrations (5 microM). The action of BQ was almost identical to that of the established Ca2+-ATPase inhibitor thapsigargin except that there were some intracellular stores of Ca2+ released by thapsigargin that were not released by BQ. BQ also was mitogenic for macrophages in conjunction with phorbol myristate acetate. These data suggest that BQ raises [Ca2+]i by inhibition of Ca2+-ATPases, is a comitogen, and does so at concentrations that could be achieved in vivo in the general urban population.

Topics: Animals; Benzoquinones; Calcium; Calcium Channels; Calcium-Transporting ATPases; Carcinogens; Catechols; Cells, Cultured; Dithiothreitol; Dose-Response Relationship, Drug; Enzyme Inhibitors; Glutathione; Hydroquinones; Inositol 1,4,5-Trisphosphate; Inositol 1,4,5-Trisphosphate Receptors; Macrophages, Peritoneal; Mice; Mice, Inbred C57BL; Mutagens; Receptors, Cytoplasmic and Nuclear; Sulfhydryl Reagents; Tetradecanoylphorbol Acetate; Thapsigargin