NEWLY SYNTHESIZED PHOSPHATIDYLINOSITOL PHOSPHATES ARE REQUIRED FOR SYNAPTIC NOREPINEPHRINE BUT NOT GLUTAMATE OR GAMMA-AMINOBUTYRIC-ACID (GABA) RELEASE

Newly synthesized phosphatidylinositol phosphates have been implicated in many membrane-trafficking reactions. They are essential for exocyt osis of norepinephrine in PC12 cells and chromaffin cells, suggesting a function in membrane fusion. We have now studied the role of phospha tidylinositol phosphates in synaptic vesicle exocytosis using synaptos omes. Under conditions where phosphorylation of phosphatidylinositols is blocked, norepinephrine secretion was nearly abolished whereas glut amate and GABA release was still elicited. Thus phosphatidylinositides are essential only for some membrane fusion reactions, and exocytotic release mechanisms differ between neurotransmitters.