Accumulation and metabolism of pipecolic acid in the developing brain of the mouse

In newborn mice, following i.p. injections of D,L-[3H]PA (pipecolic acid, 28 micrograms/kg), accumulation of radioactivity continues to increase up to 24 h. In adults, radioactivity peaks at 5 min and remains approximately constant up to 5 h, and then declines slowly to 24 h. Fifteen-day-old mice follow the newborn pattern, while 30-day-old mice show the same trend as the adult. Radioactivity in plasma shows essentially the same pattern of accumulation in adult and newborn animals with some quantitative differences. Secretion of radioactivity in the urine is significantly higher in the adult than in the newborn during the interval between 10 min and 5 h. Accumulation of radioactivity at 24 h in the newborn brain shows a preferential localization to the olfactory bulb, the anterior telencephalon and the diencephalon. Two hours after the i.p. injection, approximately 70% of the radioactivity recovered in brain is due to PA. This percentage increases to 75% and 87% at 5 and 24 h respectively. Alpha-aminoadipic acid (alpha-Aaa) a major metabolite of PA was identified in brain extracts at 5 h. The maximal formation of alpha-Aaa in relation to PA occurs approximately at 5 h. No other brain metabolites of PA could be identified with this chromatographic system. The present results show that access of PA to the brain is easier in the newborn mouse than in the adult. In addition, our results demonstrate, for the first time, the presence of PA metabolism in the newborn mouse.