Alterations in acetylcholine metabolism in rat striatal slices by a 4-methyl piperidine analog of hemicholinium-3.
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.
Tedford
C E
CE
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City.
Flynn
J R
JR
Bhatnagar
R K
RK
Cannon
J G
JG
Long
J P
JP
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002794:Choline / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D006426:Hemicholinium 3 / Q000031:analogs & derivatives* / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship
D001713:Biphenyl Compounds; D010880:Piperidines; D006426:Hemicholinium 3; C001771:4,4'-(2-(4-methylpiperidyl)-1-hydroxyethyl)biphenyl; D002794:Choline; D000109:Acetylcholine; D011188:Potassium