A possible mechanism for the hypoxia-hypoglycemia-induced release of excitatory amino acids from cultured hippocampal astrocytes.
In order to elucidate the mechanism of release of excitatory amino acid (EAA) induced by hypoxia-hypoglycemia (in vitro ischemia) from cultured hippocampal astrocytes, we compared the EAA release by in vitro ischemia with those by other treatments. The EAA release induced by in vitro ischemia treatment was rapid and reversible. The amount of released aspartate was comparable to that of glutamate, although the endogenous content of aspartate was one sixth that of glutamate. High-K (100 mM) treatment and the addition of 5 mM NaCN induced a rapid EAA release and the glutamate release was much greater than aspartate. Addition of 5 mM iodoacetate, a glycolysis inhibitor, induced a slow EAA release, and the amount of released aspartate was much higher than that of glutamate. On the other hand, the in vitro ischemia treatment and the addition of 5 mM NaCN induced only 20% reduction in ATP content for initial 5 min, whereas the addition of 5 mM iodoacetate induced a marked reduction. Our data suggest that ischemia-induced EAA release from astrocytes is a complex process in which local energy failure, inhibition of glycolysis, and depolarization of the cell membrane are involved.
Ogata
T
T
Department of Physiology, Ehime University, School of Medicine, Japan.
Nakamura
Y
Y
Tsuji
K
K
Shibata
T
T
Kataoka
K
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D018846:Excitatory Amino Acids / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism*; D007003:Hypoglycemia; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D007700:Kinetics; D010477:Perfusion / Q000295:instrumentation / Q000379:methods; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D012966:Sodium Cyanide / Q000494:pharmacology; D013997:Time Factors
D018846:Excitatory Amino Acids; D007461:Iodoacetates; D000255:Adenosine Triphosphate; D012966:Sodium Cyanide; D011188:Potassium; D019807:Iodoacetic Acid