Acetylcholine metabolism in the central nervous system

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Abstract
Glucose at low conens., e.g., below 20 mg. per 100 g. will bring about the synthesis of acetylcholine in intact rat brain slices. Fructose and galactose have relatively small effects (that of fructose being doubtful) in securing acetylcholine synthesis, but mannose has an activity approaching that of glucose. The failure of Stedman and Stedman to confirm the effect of glucose in enhancing acetylcholine production by brain is shown to be due to the limitations of their exptl. technique. The rate of formation of acetylcholine in brain tissue using the technique of Stedman and Stedman is much less than that obtained when intact rat brain slices respire in a bicarbonate-glucose medium containing 0.03 [image] K+. Preformed "bound" acetylcholine exists in brain tissue freshly obtained from the animal and the suggestion that it does not exist is based upon insufficient exptl. evidence. The effect of ether in enhancing acetylcholine formation in minced brain tissue when incubated at 37[degree] in the absence of an aq. medium is confirmed. Ether is highly inhibitory to acetylcholine formation in brain tissue examined in a phosphate- or bicarbonate-Locke medium. It is less toxic when small quantities are macerated with brain in the absence of an aqueous medium. In brain suspensions in aq. media both ether and chlorofrom break down "bound" into free acetylcholine, the reaction taking place quickly (5 min.) at room temp. The accelerating action of ether on acetylcholine formation in minced brain, in the absence of an aq. medium, lies entirely with the production of free acetylcholine, the amt. of bound ester formed being diminished in quantity. The accelerating action of ether is diminished or removed by the addition to the tissue of 0.02 [image] Ca++. The accelerating action is also greatly diminished by carrying out the expt. under anaerobic conditions. These effects closely resemble, though on a smaller scale, the action of K+ on acetylcholine formation in brain slices. The explanation of the ether effect is similar to that advanced by Mann et al., 1939, for the accelerating action of K ions. The presence of O2 greatly increases the formation of acetylcholine in ether-treated brain suggesting that the same metabolites are responsible for the synthesis as those in brain examined under more physiological conditions, e.g., glucose or lactic acid.