CEREBRAL UPTAKES AND EXCHANGE DIFFUSION IN VITRO OF l‐ AND d‐GLUTAMATES

Publisher Website
Google Scholar
Abstract
Abstract— 1. Whereas exogenous l‐glutamate enters rat brain cortex slices incubated in a glucose‐physiological saline medium by both low affinity (Km= 0.7 mm) and high affinity (Km= 27−30 μM) processes, the uptake of d‐glutamate occurs only by a low affinity (Km= 2mm) system. 2. d‐glutamate appears to release l‐glutamate from incubated rat brain cortex slices only to a very small extent, whether the tissue l‐glutamate is of endogenous or exogenous origin. 3. Competitive inhibition takes place between l‐ and d‐glutamates at the low affinity carrier. This indicates that a common carrier exists for l‐ and d‐glutamates for the low affinity uptake process. 4. Apparently non‐competitive inhibition by d‐glutamate of l‐glutamate uptake occurs at the high affinity carrier, but the affinity of d‐glutamate for this carrier is about 0.4% of that of l‐glutamate. 5. Both d‐, and l‐glutamate exchange freely with labelled d‐glutamate taken up by preliminary incubation of the brain slices with this amino acid. Whereas l‐glutamate exchanges freely with labelled l‐glutamate taken up by preliminary incubation, d‐glutamate shows little or no exchange. 6. The uptake of labelled d‐glutamate by exchange diffusion into brain slices previously loaded with unlabelled d‐glutamate proceeds by a low affinity system. Therefore, the process of exchange diffusion does not necessarily involve a high affinity uptake component. 7. Whereas ouabain suppresses both high and low affinity concentrative uptakes of l‐ and d‐glutamate it has little apparent effect on the exchange diffusion process. 8. Sensitivity to tetrodotoxin of evoked release of l‐ and d‐glutamates, taken up by brain slices by preliminary incubation with these amino acids, indicates that the major proportion of the uptake of exogenous l‐ or d‐glutamate proceeds into non‐neuronal structures (presumably the glia). 9. At 0°C non‐carrier mediated (passive) diffusion of labelled d‐ and l‐glutamate takes place in brain slices.