Characterization of D-aspartic acid uptake by rat hippocampal slices and effect of ischemic conditions.
The cellular uptake of D-aspartic acid (D-Asp) as a model compound for glutamic acid transport was studied in rat hippocampal slices. D-Asp is accumulated by both Na(+)-dependent and Na(+)-independent processes in hippocampal slices, and both processes are dependent on temperature. The Na(+)-dependent uptake is assumed to be high in affinity (apparent Km = 0.17 mM), but low in capacity, whereas the Na(+)-independent uptake is much lower in affinity (Km = 2.86 mM), but higher in capacity. L-Aspartic acid, L-glutamic acid, dihydrokainic acid, and threo-3-hydroxy-DL-aspartic acid markedly inhibited the uptake of D-Asp with Na+ in the medium, whereas D-glutamic acid, glycine, and L-lysine had no significant effect. The Na(+)-dependent uptake of D-Asp was significantly reduced under "hypoglycemic," "anoxic," and "ischemic" conditions, whereas the Na(+)-independent uptake was unaffected. Metabolic inhibitors such as NaCN and ICH2COOH significantly inhibited the Na(+)-dependent uptake, but not the Na(+)-independent uptake. These results suggest that the Na(+)-dependent component of D-Asp transport in rat hippocampal cells is inactivated under ischemic conditions, whereas the Na(+)-independent component is unaffected.
Kuwahara
O
O
Second Division, School of Pharmacy, Hokuriku University, Ishikawa, Japan.
Mitsumoto
Y
Y
Chiba
K
K
Mohri
T
T
D000818:Animals; D001224:Aspartic Acid / Q000493:pharmacokinetics*; D001692:Biological Transport / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D005971:Glutamates / Q000493:pharmacokinetics; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000502:physiology; D013997:Time Factors; D014316:Tritium
D005971:Glutamates; D014316:Tritium; D001224:Aspartic Acid; D012964:Sodium