Effects of pyroglutamic acid on corticostriatal glutamatergic transmission

Abstract

The effects of l-pyroglutamic acid, a molecule structurally derived from l-glutamic acid (Glu), were measured on the high affinity of uptake of glutamic acid from striatal synaptosomes of the rat and on the binding of [ l- 3H]glutamic acid to striatal membranes. The results showed a competitive inhibition of the high affinity transport of glutamic acid by l-pyroglutamic acid in vitro with no effect on the uptake of γ-aminobutyric acid (GABA). An inhibition of the binding of [ l- 3H]glutamic acid to striatal membranes was also detected. Significant high affinity uptake of [ l- 3H]pyroglutamic acid was evident in synaptosomes from the striatum. A regional distribution study of the uptake processes for [ l- 3H]glutamic acid and [ l- 3H]pyroglutamic acid in different areas of the brain showed a similar distribution, suggesting that an uptake of [ l- 3H]pyroglutamic acid, although weak, occurs in glutamatergic nerve terminals. This proposal was further reinforced by measuring the effects of a large cortical lesion involving frontal and parietal areas on the uptake of [ l- 3H]glutamic acid and [ l- 3H]pyroglutamic acid in synaptosomes from the striatum. The results showed a large decrease in the uptake processes of both labelled molecules showing that the uptake of [ l- 3H]pyroglutamic acid, as for glutamic acid mainly occurred in corticostriatal nerve terminals, although other uptake sites are not excluded.