EFFECTS OF PERPHENAZINE ON THE METABOLISM OF INOSITOL PHOSPHOLIPIDS IN SK-N-BE(2) HUMAN NEUROBLASTOMA-CELLS

Administration of myo-[H-3]inositol to SK-N-BE(2) human neuroblastoma cells for 24 hr resulted in equilibrium labelling of phosphatidylinosi tol (PI), phosphatidylinositol 4-phosphate (PIP) and phosphatidylinosi tol 4,5-bisphosphate (PIP2), as well as in retention of a large intrac ellular pool of free myo-[H-3]inositol. Equilibrium labelling was no l onger observed when cells were treated for 2 hr with 20 mu M perphenaz ine (PPZ) in label-free medium; under these conditions, myo-[H-3]inosi tol from the retained intracellular pool was incorporated into PI and PIP but not into PIP2. Analysis of water-soluble myo-[H-3]inositol der ivatives and inositol 1,4,5-trisphosphate mass determination indicated that PPZ did not stimulate phosphoinositide hydrolysis by phospholipa se C. These results indicate that PPZ raises PI and PIP levels, wherea s it is ineffective in expanding the PIP2 pool. The latter effect is n ot due to a concomitant synthesis and hydrolysis of this lipid.