Phosphoinositide-derived diacylglycerol conversion to phosphatidic acid is a receptor-dependent and compartmentalized phenomenon in human neuroblastoma.
We report that upon muscarinic stimulation of SK-N-BE(2) human neuroblastoma cells, the extent of phosphoinositide-derived diacylglycerol (DG) conversion to phosphatidic acid (PA), operated by a DG kinase, is dependent on the potency of receptor stimulation and correlates with the reduction of phosphatidylinositol 4,5-bisphosphate mass. Evidence is provided that agonist-evoked Ca2+ mobilisation or protein kinase activation are not key events in triggering receptor-generated DG conversion to PA; furthermore, the phenomenon is compartmentalized, namely it occurs within a topologically restricted area that is poorly accessible to DG artificially generated by cell treatment with bacterial phosphatidylinositol-specific phospholipase C. Possible mechanisms driving regulation of the DG kinase operating in the transduction system investigated are discussed.
Limatola
C
C
Department of Biology, University of Rome Tor Vergata, Italy.
Pacini
L
L
Ricci
I
I
Spinedi
A
A
D002217:Carbachol / Q000494:pharmacology; D004075:Diglycerides / Q000378:metabolism*; D006801:Humans; D018721:Muscarinic Agonists / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D010712:Phosphatidic Acids / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000502:physiology*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D004075:Diglycerides; D018721:Muscarinic Agonists; D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D002217:Carbachol