INCREASED INTRACELLULAR AND EXTRACELLULAR CONCENTRATIONS OF GAMMA-GLUTAMYLGLUTAMATE AND RELATED DIPEPTIDES IN THE ISCHEMIC RAT STRIATUM - INVOLVEMENT OF BETA-GLUTAMYL TRANSPEPTIDASE

The present work relates to the possibility that the ATP-independent e nzyme gamma-glutamyl transpeptidase (EC 2.3.2.2), which has been postu lated to be part of an amino acid uptake system, is active during cere bral ischemia. This was evaluated in the ischemic rat striatum by dete rmination of intra- and extracellular concentrations of gamma-glutamyl dipeptides (the products of the transpeptidation) and glutathione (th e physiological y-glutamyl donor). An ischemic period (0-30 and 31-60 min) resulted in prominent increases in the respective concentration o f extracellular gamma-glutamylglutamate (24- and 67-fold), gamma-gluta myltaurine + gamma-glutamylglycine (5.8- and 19-fold), and gamma-gluta mylglutamine (2.6- and 6.8-fold) as revealed using in vivo microdialys is. The changes coincided with increased respective extracellular conc entrations of glutamate (83- and 115-fold), taurine (17- and 25-fold), glycine (4.6- and 6.1-fold), and glutamine (1.7- and 2.1-fold). Furth ermore, under anoxic conditions in vitro (0-30 and 0-60 min), respecti ve striatal tissue concentrations were increased for gamma-glutamylglu tamate (20- and 17-fold), gamma-glutamyltaurine (6.7- and 11-fold), ga mma-glutamylglutamine (1.7- and 1.2-fold), and gamma-glutamylglycine ( 14- and 18-fold), whereas glutathione levels were, on an average, decr eased by similar to 350 mu M. In summary, gamma-glutamyl transpeptidas e is involved in de novo dipeptide synthesis in the mammalian brain du ring anoxic conditions, indicating transport of amino acids such as gl utamate.