Neuroligand-evoked calcium-dependent release of excitatory amino acids from cultured astrocytes.
The release of excitatory amino acids (EAAs) from neuron-free cultures of neocortical astrocytes was monitored using HPLC. The neuroligand bradykinin caused a dose-dependent receptor-mediated increase in release of the EAAs glutamate and aspartate from type 1 astrocyte cell cultures obtained from rat cerebral cortex. Removal of calcium from the extracellular fluid prevented the bradykinin-induced release of EAAs from astrocytes. The addition of the calcium ionophore ionomycin caused a calcium-dependent release of EAAs. Inhibitors of the glutamate transporters p-chloromercuriphenylsulfonic acid, L-trans-pyrrolidine-2,4-dicarboxylate, and dihydrokainate failed to impair the ability of bradykinin to stimulate glutamate release from astrocytes. alpha-Latrotoxin, an active compound of black widow spider venom, caused a significant increase of the release of glutamate in calcium-containing saline. In calcium-depleted saline, alpha-latrotoxin produced an initial increase in the concentration of glutamate followed by a decline in the concentration of glutamate indicating stimulation of exocytosis coupled with low calcium-induced inhibition of endocytosis. Taken together, these data suggest that astrocytes may release neurotransmitter through a mechanism that is similar to the neuronal secretory process. Given the important role of glutamate in the induction of long-term potentiation, learning, memory, and excitotoxicity, it will be important to determine external signals that control both the uptake and release of glutamate by astrocytes.
Jeftinija
S D
SD
Department of Veterinary Anatomy, Iowa State University, Ames 50011, USA.
Jeftinija
K V
KV
Stefanovic
G
G
Liu
F
F
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D018846:Excitatory Amino Acids / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D008024:Ligands; D009994:Osmolar Concentration; D051381:Rats
D018846:Excitatory Amino Acids; D008024:Ligands; D018698:Glutamic Acid; D001920:Bradykinin; D002118:Calcium