IN-VIVO ACIDOSIS REDUCES EXTRACELLULAR CONCENTRATIONS OF TAURINE AND GLUTAMATE IN THE RAT HIPPOCAMPUS

Microdialysis-perfusion of the urethane-anesthetized rat hippocampus w as performed to assess the effects of acidosis on extracellular amino acids. Perfusion with Krebs-Ringer bicarbonate buffer at pH 6.9 produc ed a selective decrease in taurine. A further reduction of pH to 6.4 i nduced diminished glutamate levels. The Cl-/HCO3- exchange inhibitor 4 ,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS) did not affect interstitial taurine during perfusion, but there was a rebound increa se in taurine levels upon withdrawal of the agent. In contrast, glutam ate concentrations were elevated during DIDS administration, and decre ased upon reperfusion with standard buffer. The reduction of extracell ular taurine and glutamate concentrations caused by low pH was inhibit ed by DIDS. The results suggest that taurine and glutamate uptake and/ or release in vivo is pH-dependent, and that the effects of acidosis p ossibly are mediated by the Cl-/HCO3- antiporter. The decrease in extr acellular glutamate brought about by low pH may have pathophysiologic implications in conditions associated with disturbed pH homeostasis su ch as cerebral ischemia and spreading depression. (C) 1994 Wiley-Liss, Inc.