Transient treatments with L-glutamate and threo-beta-hydroxyaspartate induce swelling of rat cultured astrocytes.
We characterized swelling of rat cultured astrocytes induced by L-glutamate and its analogues. Among L-glutamate receptor agonists, L-glutamate, L-aspartate, L-cysteic acid, DL-homocysteic acid, quisqualate and (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD) increased astrocytic intracellular volume (3H-OMG space), while kainate, and N-methyl-D-aspartate did not. Threo-beta-hydroxyaspartate (TBHA), D-aspartate and L-trans-pyrrolidine-2,4-dicarboxylic acid, high-affinity substrates for Na+-dependent L-glutamate transporters, increased astrocytic 3H-OMG space. L-Glutamate (0.5 mM) increased astrocytic 3H-OMG space to 300% of control in 40-60 min. The increase in 3H-OMG space by 1 mM TBHA was comparable to the L-glutamate-induced one. After a 10 min-exposure to 0.5 mM L-glutamate, astrocytic 3H-OMG space was further increased to 200% even in the absence of L-glutamate. Astrocytes transiently exposed to L-glutamate did not increase their cell volume in K+-free medium and in the presence of 1 mM ouabain, a Na+-K+ ATPase inhibitor. The increase after a transient exposure was also observed by a treatment of 1 mM TBHA, but not by 0.5 mM quisqualate. These results suggest that the volume increases after a transient treatment are mediated by activation of Na+-dependent L-glutamate transporter.
Koyama
Y
Y
Molecular and Neuropharmacology Laboratory, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Ishibashi
T
T
Okamoto
T
T
Matsuda
T
T
Hashimoto
H
H
Baba
A
A
D019325:3-O-Methylglucose / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000187:drug effects; D018698:Glutamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D007700:Kinetics; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY
D019325:3-O-Methylglucose; C011274:3-hydroxyaspartic acid; D001224:Aspartic Acid; D018698:Glutamic Acid; D016318:Quisqualic Acid