BIOCHEMICAL CHARACTERISTICS OF GAMMA-GLUTAMYL-TRANSPEPTIDASE IN CAPILLARIES FROM ENTORHINOHIPPOCAMPAL COMPLEX OF QUINOLINATE-LESIONED RAT-BRAIN

Quinolinic acid (QUIN) is an endogenous excitotoxic agonist of the N-m ethyl-D-aspartate (NMDA) type of glutamate receptor, which causes slow ly progressing degeneration of vulnerable neurons in some brain region s. Using changes in the activity of membrane-bound gamma-glutamyl tran speptidase (GGT) as a marker of cell damage, we found a significant de crease of this enzyme activity, which was preferentially located in th e ipsilateral hippocampal formation and entorhinal cortex, 4 d after t he unilateral intracerebroventricular (icy) injection of 0.5 mu mol QU IN. The dose of QUIN divided into two half-doses injected bilaterally led to a symmetrical decline of GGT activity in hippocampal areas. The lesion was characterized by a suppression of GGT activity in hippocam pal and entorhinal capillaries, corresponding to 60 and 81% of their i nitial value, respectively, but no significant changes were ascertaine d in synaptosomal membranes. The changes in the activity of capillary GGT were associated with the decrease of apparent maximal velocity V-m ax(app), whereas apparent Michaelis constant K-m(app) (0.69-0.79 mM) r emained unaffected. Ln the nonlesioned brain, concanavalin A (Con A) a ffinity chromatography revealed five glycoforms of synaptosomal GGT in contrast to only one found in hippocampal and entorhinal capillaries. The results document that neither the saccharide moiety of GGT nor th e value of enzyme K-m(app) is significantly affected by the QUIN-induc ed lesion of the rat brain. However, the suppression of GGT activity, which is accompanied by a decease in the value of V-max(app) in brain microvessels, may suggest dysfunction of the blood-brain barrier (BBB) in the QUIN-injuried rat brain.