Effects of L-dopa on lysine compartmentation and protein synthesis in rat brain

Abstract

The effect of L-dopa on rat brain protein synthesis was examined by studying the effect of the drug on the incorporation of radioactive amino acids into TCA-precipitable material. In the majority of experiments trace quantities of either L-[3,4(n)-H] valine or L-[4,5-3H] lysine were administered subcutaneously. Incorporation was expressed in terms of l) the relative incorporation (Irel) defined as the final TCA-insoluble radioactivity divided by the final TCA-soluble radioactivity, and 2) the apparent incorporation (I app) defined as the final TCA-insoluble radioactivity divided by the final specific activity of the soluble amino acid pool. It is shown that Irel is not, in general, a reliable index of rates of protein synthesis.L-dopa (500mg/kg,ip), administered 45 min previously, had no significant effect on either the apparent incorporation of L-[3H] valine, measured after a 15 min incorporation period, or that of L-[3H] lysine, measured after a 7.5 min incorporation period. The drug did, however, cause a significant 55-59% decrease in the apparent incorporation of L-[3H] lysine measured after a 15 min labelling period. Computer simulation was used to demonstrate that these results can be quantitatively accounted for if it is assumed that L-dopa has no effect on brain protein synthesis but does affect precursor lysine compartmentation. Temperature controlled experiments were performed in order to rule out the possibility that the difference between the effect of L-dopa on lysine and valine incorporation arose artifactually through the failure to control ambient temperature. Further, in order to obtain more reliable estimates of rates of brain protein synthesis, in two of these experiments, rats were given a quantity of L-[U-14C] valine sufficient to maintain a constant precursor specific activity throughout the incorporation period. The results confirmed those obtained at room temperature using trace quantities of labelled amino acids. While the possibility that L-dopa has a small inhibitory effect on brain protein synthesis could not be ruled out, it was concluded that a drug-induced effect on precursor lysine compartmentation was mainly responsible for the gross inhibition of lysine incorporation observed in some experiments. Preliminary experiments indicated that a similar effect may occur in rat liver.