TAURINE RELEASE EVOKED BY NMDA RECEPTOR ACTIVATION IS LARGELY DEPENDENT ON CALCIUM MOBILIZATION FROM INTRACELLULAR STORES

It is known that the activation of N-methyl-D-aspartate (NMDA) recepto rs leads to an increase in extracellular taurine concentration in diff erent brain regions. The mechanism that mediates this effect is not to tally understood. In this study, rat hippocampal slices were used to d etermine the dependence of NMDA-induced taurine release on extracellul ar calcium and/or on calcium mobilization from intracellular stores. N MDA was administered through a microdialysis probe inserted into the s lice, at the level of CA1 stratum radiatum, which was also used to col lect amino acids from the extracellular space. Field potentials evoked by stimulation of the Schaffer collaterals and recorded in the stratu m pyramidale of CA1 were used as a control of NMDA receptor activation . NMDA induced a marked increase in extracellular taurine levels and a decrease in field potential amplitude, and both effects were suppress ed in the presence of MK-801, a blocker of the NMDA receptor-linked ch annel. Dantrolene, an inhibitor of calcium release from intracellular stores, partially inhibited the extracellular taurine increase, while 2-nitro-4-carboxyphenyl-N,N-diphenyl carbamate (NCDC), an inhibitor of phosphatidylinositol-specific phospholipase C activation, had no effe ct. Removal of extracellular calcium diminished, but did not abolish, the extracellular taurine increase caused by NMDA. The remaining tauri ne response was totally suppressed by dantrolene, and also by NCDC. Th ese results demonstrate that the release of taurine induced by NMDA re ceptor activation is triggered by the increase in cytoplasmic calcium concentration. We suggest that, under physiological conditions, calciu m influx provides the signal for NMDA-induced taurine release, which i s amplified by calcium-dependent calcium mobilization from intracellul ar stores. In the absence of extracellular calcium, NMDA is still able to evoke taurine release through a mechanism that implies calcium rel ease from inositol 1,4,5-trisphosphate-sensitive stores.