Electrophoretic study of pipecolic acid, a biogenic imino acid, in the mammalian brain

Pipecolic acid (PA), one of the imino acids, is a normal constituent in the mammalian brain. It is said that PA is a major intermediate of lysine metabolism in the rat brain. Biochemical studies have suggested that PA may be involved in the regulation of synaptic mechanism in the CNS. Moreover, the pathophysiological significance of PA has been also suggested by some investigators. However, there has so far been no good evidence based on the comprehensive electrophysiological experiments. Using unit recording and microelectrophoretic technique, the action of PA on single neuron activities in the rat brain was examined. PA depressed the firing of 88 out of 115 cortical neurons tested. Only 2 were excited and 25 remained unaffected. All the identified hippocampal pyramidal neurons examined were uniformly inhibited. It has been reported that PA inhibits the uptake of GABA into the brain slices and enhances the release of GABA from the slices. Thus, it is likely that the inhibitory response due to PA may have some connections with GABAergic transmission. On the other hand, it remains to be clarified whether the specific PA sensitive receptors exist in the brain. Our findings provide a clue to the elucidation of the presumed synaptic involvement of PA in the CNS.