[Release of glutamate from cytosol of synaptosomes under conditions of experimental hypergravity].
The release of L-[14C]glutamate via Na+-dependent glutamate transporters functioned in the reverse mode was investigated in cortical synaptosomes under centrifuge-induced hypergravity. The protonophore carbonyl cyanide-p-trifluoromethoxyphenyl-hydrazon (FCCP) induced increase in [Na+]i, depolarized the plasma membrane, dissipated the proton gradient across synaptic vesicles and mitochondrial membrane, caused a fall in both the ATP level and the ATP/ADP ratio. 35 mM KCl-stimulated L-[14C]glutamate release from synaptosomes preliminary treated with 1 microM FCCP considerably increased from 27.0+/-2.2 % to 35.0+/-2.3 % of total accumulated synaptosomal label after centrifuge-induced hypergravity as compared to control animals (P< or =0.05). We found the competitive nontransportable glutamate transporter inhibitor DL-threo-beta-benzyloxyaspartate to inhibit FCCP and high KCL-stimulated release of L-[14C]glutamate. The release would be expected to occur via plasma membrane glutamate transporters. Transportable inhibitor of glutamate transporters-DL-threo-beta-hydroxyaspartate (DL-THA) induced heteroexchange of L-[14C]glutamate from enlarged by FCCP cytosolic pool of the neurotransmitter. DL-THA-evoked release of L-[14C]glutamate was also increased significantly after hypergravity. Combined application of KCl, DL-THA and FCCP unmasked dramatic changes in the activity of the glutamate transporters functioning in the reverse mode after centrifuge-induced G-loading.
Borisova
T A
TA
Krysanova
N V
NV
D000818:Animals; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D018471:Hypergravity / Q000009:adverse effects*; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D007476:Ionophores; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D018698:Glutamic Acid; D011189:Potassium Chloride