An inositol tetrakisphosphate-containing phospholipid in activated neutrophils

Inositol (1,4,5)triphosphate (InsP3) and tetrakisphosphate (InsP4) have been observed in a variety of cell types and have been proposed to play roles in the receptor-mediated rise in intracellular Ca2+ (refs 2, 3). Recently, they have been shown to act synergistically in the activation of a Ca2+-dependent K+ channel in lacrimal acinar cells. InsP3 is the product of phospholipase C (PLC) action on phosphatidylinositol 4,5-bisphosphate (PtdInsP2) whereas InsP4 is believed to arise from phosphorylation of InsP3 by a cytosolic kinase. Although sought as a source for InsP4, PtdInsP3 has not been identified in any specific cell type. There were early reports of InsP4-containing phospholipids in crude extract from bovine brain, but this finding was later withdrawn. Recently, however, a membrane-bound enzyme (Type 1 PI kinase) which adds phosphate onto the 3 position of inositol phospholipids has been identified and the phosphatidylinositol-3-phosphate (PtdIns(3)P) product characterized. This suggests that several forms of phosphoinositides may exist and could be precursors for some of the variety of soluble inositol phosphate products which have been reported in recent years. Here we report the appearance of another novel phosphoinositide containing four phosphates, phosphatidylinositol trisphosphate (PtdInsP3) which we find only in activated but not in unstimulated neutrophils from human donors.