An inositol tetrakisphosphate-containing phospholipid in activated neutrophils

Abstract

Inositol (l,4,5)trisphosphate (InsP₃)¹ and tetrakisphosphate (InsP₄)² 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 cells³. 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 kinase⁴. Although sought as a source for InsP₄, PtdInsP₃ has not been identified in any specific cell type². There were early reports of InsP₄-containing phospholipids in crude extract from bovine brain⁵, but this finding was later withdrawn⁶. Recently, however, a membrane-bound enzyme (Type 1 PI kinase) which adds phosphate onto the 3 position of inositol phospholipids has been identified⁷ 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.