Glucocorticoids increase extracellular [3H]D-aspartate overflow in hippocampal cultures during cyanide-induced ischemia.
Glucocorticoids (GCs), the adrenal steroid hormones secreted during stress, exacerbate neuronal death in the hippocampus during ischemia. Since ischemia brain damage is ascribed to an elevated level of extracellular excitatory amino acids (EAAs), this study was undertaken to investigate the effect of GCs on EAA homeostasis in hippocampal cell cultures during the insult of cyanide exposure. Using D-[2,3-3H]aspartic acid ([3H]D-Asp) as a tracer, we found that corticosterone (CORT, the physiological GC in rats) increased the accumulation of extracellular [3H]D-Asp by 25% in hippocampal cultures during cyanide-induced ischemia. CORT had no effect on the release of [3H]D-Asp. Instead, analysis of [3H]D-Asp uptake kinetics indicates that CORT decreased the maximum uptake rate and the Michaelis constant by 44% and 50%, respectively, in cells treated with cyanide. It is concluded that, during cyanide-induced ischemia, CORT might enhance extracellular overflow of [3H]D-Asp by decreasing its uptake, thereby endangering neurons.
Chou
Y C
YC
Department of Biological Sciences, Stanford University, CA 94305.
Lin
W J
WJ
Sapolsky
R M
RM
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D002545:Brain Ischemia / Q000139:chemically induced / Q000378:metabolism*; D003486:Cyanides; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
D003486:Cyanides; D005938:Glucocorticoids; D001224:Aspartic Acid