Release of glutamate and aspartate from CA1 synaptosomes: selective modulation of aspartate release by ionotropic glutamate receptor ligands.
Synaptosomes prepared from area CA1 of the rat hippocampus were used to determine (a) whether Schaffer collateral-commissural-ipsilateral associational terminals release both aspartate and glutamate in a Ca(2+)-dependent manner when reuptake of released glutamate is minimal and (b) whether autoreceptor mechanisms described in CA1 or hippocampal slices could reflect direct actions of glutamate receptor ligands on the synaptic terminal. When challenged for 1 min with either 25 mM K+ or 300 microM 4-aminopyridine, CA1 synaptosomes released both glutamate and aspartate in Ca(2+)-dependent manner. The glutamate/aspartate ratio was approximately 5:1 in each case. K(+)-evoked glutamate release was unaffected by ligands active at NMDA or (RS)-alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionate (AMPA) receptors. Unlike glutamate release, the release of aspartate was enhanced by NMDA, and this effect was blocked by D-2-amino-5-phosphonovalerate (D-AP5). Kainate selectively depressed and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) selectively increased the K(+)-evoked release of aspartate. AMPA enhanced aspartate release, like the antagonist CNQX. When applied in the presence of diazoxide, which blocks the desensitization of AMPA receptors, AMPA and kainate both depressed aspartate release. These findings support the view that Schaffer collateral-commissural-ipsilateral associational terminals release aspartate as well as glutamate and that these two release processes are regulated by different autoreceptor mechanisms.
Zhou
M
M
Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710.
Peterson
C L
CL
Lu
Y B
YB
Nadler
J V
JV
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D002118:Calcium / Q000502:physiology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008024:Ligands; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism*
D008024:Ligands; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D001224:Aspartic Acid; D018698:Glutamic Acid; D011188:Potassium; D002118:Calcium