Evidence of glutathione transporter in rat brain synaptosomal membrane vesicles

Glutathione (GSH) transport was studied in synaptosomal membrane vesicles ( SMV) of rat cerebral cortex. The present study shows that GSH uptake into S MV occurs very quickly in a time-dependent manner into an osmotically activ e intravesicular space. The initial rate of transport followed Michealis-Me nten saturation kinetics with a K-m 4.5 +/- 0.8 mu M that shows a high affi nity of the transporter for GSH. Therefore GSH uptake in SMV occurs by a me diated transport system which can be activated by either an inward gradient of cations, like Na+ or K+, or membrane depolarization. These results, tog ether with those obtained by valinomycin-induced K+ diffusion potential, in dicate that GSH synaptosomal transport is electrogenic by a negative charge transfer. The increase of GSH uptake measured by trans-stimulation experim ents confirms a GSH bidirectional mediated transport which seems susceptibl e of modulation by changes in ionic fluxes and in the membrane potential. T hese results may indicate a possible involvement of this transporter in the role suggested for GSH in synaptic neurotransmission; also considering tha t GSH precursor of neuroactive aminoacids (glyeine, glutamate), may contrib ute to regulate their level in synapses. Finally, a GSH transporter in syna ptosomes may contribute to maintaining the GSH homeostasis in cerebral cort ex, where decreases of GSH levels have been related to susceptibility to ne uropathologies. (C) 1999 Elsevier Science Ltd. All rights reserved.