The Independency of Choline Transport and Acetylcholine Synthesis

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Abstract
The coupling of choline transport to acetylcholine [ACh] synthesis was investigated by measurement of the isotopic dilution of a pulse of [3H]choline during its incorporation into the recently synthesized ACh of [guinea pig] cerebral cortex synaptosomes. Recently synthesized ACh was identified as that containing 14C-labeled precursors introduced by a preincubation before the pulse. When [14C]glucose was used to label acetyl-CoA coupling ratios (calculated as the inverse of the dilution of extracellular [3H]choline during its incorporation into [3H]ACh) of .apprx. 0.05-0.2 were found at a choline concentration of 1 .mu.M, rising to 0.5 at choline concentrations of 10-50 .mu.M. Experiments using [14C]choline as a precursor gave similar results. The isotopic dilution did not occur extrasynaptosomally and was not affected by low glucose concentrations. Coupling ratios were always less than unity and rose as the choline concentration increased. Choline transported into the nerve terminal has no privileged access to choline acetyltransferase. The results can be explained by a rate-controlling transport of choline into the terminal followed by its rapid acetylation rather than any linkage or coupling of the 2 processes.