Summary
The present study investigates the effects of phenylsuccinate (PS), an inhibitor of the mitochondrial ketodicarboxylate carrier (KCC), on release ofγ-aminobutyric acid (GABA), glutamate (Glu), glutamine (Gln), and glycine (Gly), induced by potassium chloride (KCl) and by cardiac arrest caused by a halothane overdose. Microdialysates were collected from the hippocampus of anaesthetized rats, and analyzed by HPLC. Continuous perfusion of 50 mM PS through the dialysis probe, reduces release of GABA induced by KCl (50 mM for 10 min through the dialysis probe) by up to 72%. In addition, PS abolished KCl-induced release of Glu. Release of GABA during cardiac arrest was not reduced by PS, whereas PS reduced release of Glu in the early stage of cardiac arrest. PS furthermore increased the basal level of Gln, and reversed a decrease of Gln induced by cardiac arrest.
It is proposed that the KCC is present in GABA'ergic neurons of the rat hippocampus, and that GABA, released by KCl, can be synthesized in a KCC dependent manner. It is also suggested that ischemia-induced release of GABA, to some extent, has a non-transmitter origin. The results furthermore indicate that uptake of Gln into GABA'ergic and Glu'ergic neurons is not regulated by simple demand mechanisms.
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Abbreviations
- PS:
-
phenylsuccinate
- KCC:
-
ketodicarboxylate carrier
- GABA:
-
γ-aminobutyric acid
- Glu:
-
glutamate
- Gln:
-
glutamine
- Gly:
-
glycine
- α-KG:
-
α-ketoglutarate
- Mal:
-
malate
- KRB-buffer:
-
Krebs-Ringer bicarbonate-buffer
- HPLC:
-
high pressure liquid chromatography
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Cobo, M., Bruhn, T., Berg, M. et al. Phenylsuccinate reduces KCL-induced release of GABA evidence for the participation of the ketodicarboxylate carrier in the biosynthesis of transmitter-GABA. Amino Acids 5, 377–388 (1993). https://doi.org/10.1007/BF00806956
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DOI: https://doi.org/10.1007/BF00806956