Uptake, Release, and Metabolism of D- and L-α-Aminoadipate by Rat Cerebral Cortex

Abstract: Accumulation of L-α-aminoadipate by rat cerebral cortical slices is a stereospecific and Na⁺-dependent process. The uptake of this compound is also temperature-dependent, with a K_m , of 1.6 × 10⁻⁴M for the high-affinity system. D-α-Aminoadipate has characteristics similar to those displayed by the L-isomer but to a lesser degree. L-Glutamate and L-aspartate inhibit the uptake of L-α-aminoadipate. D- and L-α-Aminoadipate are, respectively, weak uncompetitive and weak competitive inhibitors for the uptake of L-glutamate and L-aspartate. Both enantiomers inhibit GABA uptake but in quite different ways. The release of L-α-aminoadipate from the cerebral cortical slices is stimulated by a high concentration of K⁺ ions in the presence of Ca²⁺ in the perfusion buffer; the D-isomer displays this property to a lesser degree. The omission of Ca²⁺ markedly reduces the release of these two compounds. Less than 10% of the preloaded D- and L-α-aminoadipate are metabolized by the cerebral cortex during 40 min of superfusion. The possibility of L-α-aminoadipate as a neurotransmitter candidate is discussed.