Effects of the inhibitors on glutamate uptake by nerve terminals after exposure of rats to centrifuge-induced hypergravity.
L-[14C]glutamate uptake process by nerve terminals has been investigated using glutamate analogs (nontransportable and transportable inhibitors of glutamate transporters) as tools. The effects of L-threo-beta-benzyloxyaspartate (DL-TBOA) and L-threo-beta-hydroxyaspartate (L-TBHA) on uptake of L-[14C] glutamate have been evaluated after exposure of rats to centrifuge-induced hypergravity. Both glutamate analogs potently inhibited L-[14C] glutamate uptake in dose-dependent manner. The IC50 values for DL-TBOA (nontransportable analog) calculated on the basis of curves of non-linear regression kinetic analysis was 18 +/- 2 micromoles and 11 +/- 2 micromoles (P < or = 0.05) before and after exposure to artificial gravity, respectively. Inhibition caused by 10 micromoles DL-TBOA was significantly increased from 38.0 +/- 3.8% in control group to 51.0 +/- 4.1% in animals, exposed to hypergravity (P < or = 0.05). L-TBHA, transportable analog, exhibited similar inhibitory characteristics.
Borisova
Tatiana
T
The Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, Kiev, Ukraine. tborisov@biochem.kiev.ua
Himmelreich
Nina
N
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002498:Centrifugation; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D018471:Hypergravity; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects*
C120673:benzyloxyaspartate; C011274:3-hydroxyaspartic acid; D001224:Aspartic Acid; D018698:Glutamic Acid