BIOCHEMICAL STUDIES ON CHLORPROMAZINE: 2. EFFECTS OF CHLORPROMAZINE ON INCORPORATION INTO PROTEINS, AND BREAKDOWN OF GLYCINE-1-C14BY ISOLATED RAT BRAIN CORTEX

Abstract

Glycine is decomposed in rat brain cortex to yield carbon dioxide. This process, in which C14O2is formed from glycine-1-C14, is markedly stimulated by the presence of 10 mM glucose, the rate of production of C14O2being increased at least threefold. The presence of succinate exercises a much smaller stimulation of C14O2formation. The addition of KCl (0.1 M) or of 2,4-dmitrophenol (0.025 mM), whilst stimulating the rate of oxygen uptake, does not increase the rate of C14O2formation from glycine-1-C14. The addition of K+tends to diminish the rate. The process of glycine-1-C14breakdown to C14O2is almost insensitive to chlorpromazine, under the given experimental conditions, until relatively high concentrations (e.g. 0.6 mM) are used. The presence of chlorpromazine, however, brings about an inhibition of the rate of glycine-1-C14incorporation into rat brain cortex proteins, an inhibition of 20% being recorded at a concentration of the drug (0.2 mM) that has little or no effect on the respiration of the brain or on the rate of breakdown of glycine-1-C14into C14O2. Glycine incorporation into brain cortex proteins is a process relatively sensitive to chlorpromazine, the magnitude of inhibition being of the same order as that brought about by amytal at similar concentrations. It is suggested that chlorpromazine brings about its effects by an uncoupling of phosphorylation from oxidation in brain cortex slices.