Accumulation, elimination, release and metabolism of pipecolic acid in the mouse brain following intraventricular injection
Following i.c.v. (intracerebral ventricular) injections ofd,l-[3H]pipecolic acid (PA), it is reabsorbed from the ventricles and redistributed to various brain regions. The highest accumulation is found in three brain regions ipsilateral to the injection site, hippocampus, neocortex, striatum, and in the diencephalon. Following preloading in vivo, the radioactivity is released from hippocampus slices in the perfusion medium after depolarization induced by high K+. During perfusion with a Ca++ free medium containing EGTA, a significant reduction of release is observed.
The radioactivity ofd,l-[3H]PA in the brain shows a more rapid phase of decrease from 0 to 2 hours and a slower phase from 2 to 5 hours. At 5 hours, only 28% radioactivity, represented mainly by PA, is left in the brain. Kidney secretion represents the major route of elimination of the injected PA. The presence of α-aminoadipic acid both in brain and urine was observed. Probenecid (200 mg/kg) significantly increases the accumulation of i.c.v. injectedd,l-[3H]PA in brain and kidney. The presence of a regional accumulation of PA in certain brain regions, its metabolism in brain, its enhanced retention following probenecid administration and its Ca++ dependent release following high K+ stimulation, all constitute indirect evidence for a neuronal localization of this brain endogenous iminoacid.
KeywordsBrain Region EGTA Mouse Brain Injection Site High Accumulation
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- 1.Schmidt-Glenewinkel, T., Nomura, Y., andGiacobini, E. 1977. The conversion of lysine into piperidine, cadaverine, and pipecolic acid in the brain and other organs of the mouse. Neurochem. Res. 2:619–637.Google Scholar
- 2.Giacobini, E., Nomura, Y., andSchmidt-Glenewinkel, T. 1980. Pipecolic acid: Origin, biosynthesis and metabolism in the brain. Cell. Molec. Biol. 26:135–146.Google Scholar
- 3.Nishio, H., Ortiz, J., andGiacobini, E. 1981. Accumulation and metabolism of pipecolic acid in the brain and other organs of the mouse. Neurochem. Res. 6:1235–1245.Google Scholar
- 6.Burgstahler, A. W., andAiman, C. E. 1960. A direct synthesis ofd,l-baikiain. J. Org. Chem. 25:489–492.Google Scholar
- 7.Sidman, R. L., Angevine, J. B., Jr. andPierce, E. T. 1971. Atlas of the mouse brain and spinal cord. Cambridge, Mass.: Harvard Univ. Press.Google Scholar
- 9.Schmidt-Glenewinkel, T., Giacobini, E., Nomura, Y., Okuma, Y., andSegawa, T. 1978. Presence, metabolism and uptake of pipecolic acid in the mouse brain. 2nd Meet. Eur. Soc. Neurochem., Abst. 618.Google Scholar
- 10.Nomura, Y., Schmidt-Glenewinkel, T., andGiacobini, E. 1978. In vitro formation of piperidine, cadaverine and pipecolic acid in chick and mouse brain during development. Dev. Neurosci. 1:239–249.Google Scholar
- 15.Okuma, Y., Nomura, Y., andSegawa, T. 1979. The effect of piperidine and pipecolic acid on high potassium-induced release of noradrenaline, serotonin and GABA from rat brain slices. J. Pharm. Dyn. 2:261–265.Google Scholar