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 neurobl astoma cells, the extent of phosphoinositide-derived diacylglycerol (D G) conversion to phosphatidic acid (PA), operated by a DG kinase, is d ependent on the potency of receptor stimulation and correlates with th e reduction of phosphatidylinositol 4,5-bisphosphate mass. Evidence is provided that agonist-evoked Ca2+ mobilization or protein kinase acti vation are not key events in triggering receptor-generated DG conversi on to PA; furthermore, the phenomenon is compartmentalized, namely it occurs within a topologically restricted area that is poorly accessibl e to DG artificially generated by cell treatment with bacterial phosph atidylinositol-specific phospholipase C. Possible mechanisms driving r egulation of the DG kinase operating in the transduction system invest igated are discussed.