Influence of choline, hemicholinium-3 and naphthylvinylpyridine on uptake and acetylation of 3H-labeled choline into hippocampus slices

Abstract

In slices of rat hippocampus the influence of choline (Ch), hemicholinium-3 (HC-3), and naphthylvinylpyridine (NVP) on the uptake of [ 3H]-Ch and its incorporation into acetylcholine (ACh) was studied. Increasing concentrations of Ch, added to the incubation medium, led to an elevation of the uptake of labeled precursor and its acetylation. The release of radioactive labeled ACh from slices of hippocampal tissue was also enhanced. A kinetic analysis of the transport of Ch revealed two distinct uptake systems for the precursor with K m -values of 0.87 μM and 30.3 μM, respectively. The uptake of tritiated Ch into hippocampal slices could be inhibited by HC-3. NVP, an inhibitor of choline acetyltransferase, reduced the uptake of Ch to a similar degree as observed by HC-3, whereas the subsequent acetylation to ACh was not affected. Using an intraventricular application of 400 nmoles unlabeled Ch, the influence of the precursor on uptake and incorporation of [ 3H]-Ch was also tested in vivo. Both the uptake of Ch and its subsequent acetylation were enhanced, whereas no changes in the ACh content of the hippocampus were observed. The data suggest that the increase of the precursor supply yields an elevation of Ch transport, its acetylation and the transmitter release.