The influence of drugs on the uptake of acetylcholine by slices of rat cerebral cortex

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Abstract
1 The acetylcholine content of cortical slices from rat brain, was determined after incubation for 30 min in a medium containing acetylcholine (4 μg/ml.). The cholinesterase activity of the slices had been inhibited by pretreatment with 3,3-dimethyl-n-butyl 2-methylphosphonofluoridate (soman). 2 Acetylcholine accumulated in the tissue slices, up to a concentration of about six times that in the medium. 3 The uptake of acetylcholine was partly inhibited by potassium in high concentrations. 4 Hemicholinium-3, O-ethyl S-diethylaminoethyl ethylphosphonothiolate, physostigmine, atropine and choline, in that order of potency, inhibited the accumulation of acetylcholine in the cortical slices, but soman and ethyl N,N-dimethyl phosphonoamidocyanate (tabun) had no effect on the uptake of acetylcholine. 5 Substances interfering with energy metabolism, such as 2,4-dinitrophenol, oligomycin, sodium azide, amylobarbitone sodium and p-chloromercuribenzoate inhibited the uptake of acetylcholine. Ouabain had little inhibitory effect. 6 In anaerobic conditions the accumulation of acetylcholine in the tissue slices was nearly blocked. 7 The uptake of acetylcholine in the tissue slices was dependent on temperature. The Q10 was about 2. 8 Autoradiography of sections from slices in which 3H-acetylcholine had accumulated showed a diffuse distribution of radioactivity in the cytoplasm of all cells. There was no visible preference for certain cells or cell structures.