Kinetics of D-aspartic acid release from rat cortical synaptosomes.

Abstract

A kinetic study has been made of the release of D-aspartate from rat cortical synaptosomes following pre-loading with labelled D-aspartate, and the results compared to a previous study of the release of the acidic amino acids glutamate plus aspartate following pre-loading with labeled L-glutamate. Qualitatively, the results of the two studies are similar. The D-aspartate taken up during the pre-load period appears to be totally releasable. However, release is greatly increased by depolarizing media. The increased rate of release induced by increasing [K]o is independent of the [Ca]o, while veratrine-induced release is inhibited by [Ca]o. Release is from more than a single compartment, since plots of the log10 of the synaptosomal D-aspartate content (calculated from the label content) as a function of the incubation time are non-linear for all incubation solutions. In the previous study which utilized L-glutamate pre-loading, the results were consistent with either a model consisting of two passive compartments (that is, synaptosomal content T as a function of time is given by Ae-Kat + Be-Kbt, in which A and B are compartment sizes, Ka and Kb are exchange constants, and t is incubation time) or a model consisting of one passive compartment (Ae-Kat) and one saturated carrier compartment (T-Kbt, in which T = total content at zero time and Kb = maximal velocity). The present results with D-aspartate also give excellent fits to these models. However, there are some quantitative differences in the estimates of the compartment sizes and exchange constants, which are obtained by optimizing the fit of the data to the equation for each model. Although most of these quantitative differences appear to be minor, one difference between the two studies is of potential significance in interpretation of the results. In the glutamate study, all depolarizing media were found to reduce the exchange constant for the carrier mechanism, while in the present study, depolarizing media were found to increase the exchange constant, with the exception of veratrine-containing medium without calcium.