Effect of phenylsuccinate on potassium- and ischemia-induced release of glutamate in rat hippocampus monitored by microdialysis.
The extracellular concentration of glutamate in rat hippocampus during physiological conditions, elevated extracellular K+ and global ischemia was followed by microdialysis and subsequent determination of glutamate by HPLC. The effect of phenylsuccinate, an inhibitor of the mitochondrial dicarboxylate carrier, was studied. It was found that while phenylsuccinate had no effect on the extracellular glutamate concentration during perfusion under physiological and ischemic conditions, the potassium-induced increase in the extracellular glutamate concentration was totally blocked by phenylsuccinate. Ischemia led to a pronounced glutamate overflow. The finding that phenylsuccinate could inhibit potassium-induced glutamate release into the extracellular space but not that induced by ischemia suggests that glutamate released under these conditions originates from different pools. Since glutamate released by a depolarizing concentration of potassium is likely to originate primarily from the transmitter pool, the ischemia-induced glutamate overflow may primarily be released from both the transmitter and the metabolic pool. This is compatible with the previous finding that phenylsuccinate specifically prevents biosynthesis of transmitter glutamate leaving the metabolic glutamate pool unaffected.
Christensen
T
T
PharmaBiotec Research Center, University of Copenhagen, Denmark.
Bruhn
T
T
Diemer
N H
NH
Schousboe
A
A
D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D029382:Dicarboxylic Acid Transporters; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects; D011188:Potassium / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D012964:Sodium / Q000502:physiology; D013386:Succinates / Q000494:pharmacology*
D002352:Carrier Proteins; D029382:Dicarboxylic Acid Transporters; D005971:Glutamates; D013386:Succinates; D018698:Glutamic Acid; C017625:2-phenylsuccinate; D012964:Sodium; D011188:Potassium