Effects of perphenazine on the metabolism of inositol phospholipids in SK-N-BE(2) human neuroblastoma cells.
Administration of myo-[3H]inositol to SK-N-BE(2) human neuroblastoma cells for 24 hr resulted in equilibrium labelling of phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2), as well as in retention of a large intracellular pool of free myo-[3H]inositol. Equilibrium labelling was no longer observed when cells were treated for 2 hr with 20 microM perphenazine (PPZ) in label-free medium; under these conditions, myo-[3H]inositol from the retained intracellular pool was incorporated into PI and PIP but not into PIP2. Analysis of water-soluble myo-[3H]inositol derivatives and inositol 1,4,5-trisphosphate mass determination indicated that PPZ did not stimulate phosphoinositide hydrolysis by phospholipase C. These results indicate that PPZ raises PI and PIP levels, whereas it is ineffective in expanding the PIP2 pool. The latter effect is not due to a concomitant synthesis and hydrolysis of this lipid.
Pacini
L
L
Department of Biology, University of Rome, Tor Vergata, Italy.
Limatola
C
C
Palma
E
E
Spinedi
A
A
D002460:Cell Line / Q000187:drug effects; D006801:Humans; D007294:Inositol / Q000032:analysis / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism*; D010546:Perphenazine / Q000494:pharmacology*; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D014316:Tritium
D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; C037178:phosphatidylinositol 4-phosphate; D014316:Tritium; D007294:Inositol; D010546:Perphenazine