Ca(2+)-dependent activation of phospholipases C and D from mouse peritoneal macrophages by a selective trigger of...

The gamma-isomer of hexachlorocyclohexane (gamma-HCCH), which displays structural homology with inositol, was found to induce an initial influx of Ca2+ in mouse peritoneal macrophages. This was responsible for Ca(2+)-induced Ca2+ release via inositol 1,4,5-trisphosphate produced by phospholipase C and resulted in a sustained increase of cytoplasmic free Ca2+ concentration ([Ca2+]i). Entry of Ca2+ evoked by gamma-HCCH also stimulated phospholipase D, as well as the generation of reactive oxygen species formed by NADPH oxidase. These data suggest that some isoform(s) of phospholipase C, and possibly phospholipase D, can be activated by strictly Ca(2+)-dependent mechanisms. They also describe a new experimental tool allowing to trigger a selective influx of Ca2+. gamma-HCCH could thus be used in further studies aimed to delineate the role of Ca2+ entry in the subsequent activation of other signalling pathways.