In vivo acidosis reduces extracellular concentrations of taurine and glutamate in the rat hippocampus.
Microdialysis-perfusion of the urethane-anesthetized rat hippocampus was performed to assess the effects of acidosis on extracellular amino acids. Perfusion with Krebs-Ringer bicarbonate buffer at pH 6.9 produced a selective decrease in taurine. A further reduction of pH to 6.4 induced 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 increase in taurine levels upon withdrawal of the agent. In contrast, glutamate concentrations were elevated during DIDS administration, and decreased upon reperfusion with standard buffer. The reduction of extracellular taurine and glutamate concentrations caused by low pH was inhibited by DIDS. The results suggest that taurine and glutamate uptake and/or release in vivo is pH-dependent, and that the effects of acidosis possibly are mediated by the Cl-/HCO3- antiporter. The decrease in extracellular glutamate brought about by low pH may have pathophysiologic implications in conditions associated with disturbed pH homeostasis such as cerebral ischemia and spreading depression.
Puka
M
M
Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, Warsaw.
Lehmann
A
A
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D017920:Antiporters / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001639:Bicarbonates / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism*; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006624:Hippocampus / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008297:Male; D017551:Microdialysis; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009997:Osmotic Pressure; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D013654:Taurine / Q000378:metabolism*
D017920:Antiporters; D001639:Bicarbonates; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D005971:Glutamates; D009419:Nerve Tissue Proteins; D017923:Sodium-Hydrogen Exchangers; D013654:Taurine; D018698:Glutamic Acid; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid