Phospholipid-derived choline intermediates and acetylcholine synthesis in mouse brain synaptosomes.

Endogenous free choline levels and acetylcholine (ACh) synthesis in nerve terminals were investigated using cerebral cortical synaptosomes of C57BL/6 mice. Endogenous choline was produced at a rate ten-fold faster than ACh to provide levels adequate for the formation of the latter. The combined pool size of the water-soluble intermediates derived from phosphatidylcholine (PhC), such as glycerophosphorylcholine (GpCh) and phosphorylcholine (PCh), increased significantly during the first 10-15 min of incubation and was always higher than that of free choline. These results most likely indicate an effective degradation of PhC by the combined action of phospholipase A2/lysophospholipase, as well as by phospholipase C in synaptosomes. ACh synthesis proceeded at a constant rate in the presence or absence of exogenous free choline (0-10 microM) and was almost entirely abolished in the presence of 10(-6) M hemicholinium-3. These results suggest that ACh is effectively synthesized by free choline generated in synaptosomes by a coupling mechanism involving the high-affinity choline uptake system. No changes in the production rates of choline and ACh were observed between adult and aged mice.