CA2-DEPENDENT ACTIVATION OF PHOSPHOLIPASE-C AND PHOSPHOLIPASE-D FROM MOUSE PERITONEAL-MACROPHAGES BY A SELECTIVE TRIGGER OF CA2+ INFLUX, GAMMA-HEXACHLOROCYCLOHEXANE()

The gamma-isomer of hexachlorocyclohexane (gamma-HCCH) which displays structural homology with inositol, was found to induce an initial infl ux of Ca2+ in mouse peritoneal macrophages. This was responsible for C a2+-induced Ca2+ release via inositol 1,4,5-trisphosphate produced by phospholipase C and resulted in a sustained increase of cytoplasmic fr ee 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 ac tivated by strictly Ca2+-dependent mechanisms. They also describe a ne w experimental tool allowing to trigger a selective influx of Ca2+. ga mma-HCCH could thus be used in further studies aimed to delineate the role of Ca2+ entry in the subsequent activation of other signalling pa thways. (C) 1994 Academic Press, Inc.