Mechanisms of Acetylcholine Synthesis: Coupling with Choline Transport

Abstract

Mechanisms regulating acetylcholine (ACh) synthesis at the cholinergic nerve terminal have not been resolved. Clearly, choline utilized in the synthesis of ACh is derived from an extraneuronal source rather than being synthesized de novo within the cholinergic neuron (12). A number of investigators have demonstrated that the supply of exogenous choline to the nerve ending by sodium-dependent high-affinity choline carriers may be both rate-limiting and regulatory in the synthesis of ACh (4, 5, 9, 14, 29, 34) with a high percentage of the transported choline being metabolized to ACh (5, 35). Contradictory evidence has, however, been presented recently indicating that in guinea-pig brain synaptosomes choline taken into the nerve ending by high- affinity choline carriers makes only a minor contribution as precursor for ACh synthesis (16, 20). Whereas it has been reported that the major source of choline for ACh synthesis is derived from preexisting cytoplasmic choline pools in guinea-pig brain synaptosomes, evidence has been presented that in rat brain synaptosomes synthesis of ACh utilizing a cytoplasmic pool of choline as precursor could not be measured (32).