Alterations in acetylcholine metabolism in rat striatal slices by a 4-methyl piperidine analog of hemicholinium-3.

Autor: Tedford, C E, Flynn, J R, Bhatnagar, R K, Cannon, J G, Long, J P
Zdroj: The Journal of Pharmacology and Experimental Therapeutics; November 1988, Vol. 247 Issue: 2 p460-465, 6p
Abstrakt: The in vitro effects of a tertiary amine, 4-methyl piperidine analog of hemicholinium-3 (A-4), were investigated on acetylcholine (ACh) metabolism in rat striatal slices. Rat striatal slices were incubated in the presence of 1.0 microM [3H]-choline in the presence or absence of 0.1 mM A-4. High pressure liquid chromatography with electrochemical detection was utilized to separate and measure total and [3H]-labeled ACh and choline. The effects of A-4 on [3H]-choline uptake, ACh and choline content, ACh release, and specific activity of ACh and choline tissue pools were investigated. Results indicated that A-4 inhibited the uptake of [3H]-choline into the striatal slices. Addition of 0.1 mM A-4 also produced a significant reduction in ACh content and ACh release and reduced the specific activity of the tissue choline and ACh pools. The effects of A-4 were more prominent upon immediate incubation than after a 60-min preincubation. These studies demonstrate that the pharmacological effects exhibited by A-4 are consistent with inhibition of choline uptake, with subsequent reduction in ACh synthesis and release.
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