[Modulating effect of glutamate transporter inhibitors on accumulation and release of the neuromediator by the brain nerve terminals in rats].
L-[14C]glutamate uptake and release processes in nerve terminals has been investigated using the nontransportable and transportable competitive inhibitors of glutamate transport as tools. The effects of DL-threo-beta-benzyloxyaspartate (DL-TBOA) and DL-threo-beta-hydroxyaspartate (DL-THA) on the accumulation of L-[14C]glutamate have been evaluated after the exposure of rats to centrifuge-induced hypergravity. Both analogs potently inhibited the L-[14C]glutamate uptake in a dose-dependent manner (100 microM glutamate, 30 s incubation period). The IC50 values for DL-TBOA calculated on the basis of curves of non-linear regression kinetic analysis was 18 +/- 2 microM and 11 +/- 2 microM (p < or = 0.05) before and after the exposure to artificial gravity, respectively. L-THA, transportable analog, exhibited similar inhibitory characteristics (18 +/- 2 and 12 +/- 2 microM, respectively). We have also demonstrated that DL-TBOA exerted slighter effect on depolarization-evoked carrier-mediated L-[14C]glutamate release in control rats in comparison with gravity-loaded ones. Thus, DL-TBOA had complex effect on glutamatergic transmission, inhibited uptake and release of L-glutamate, and perhaps, became more potent under centrifuge-induced hypergravity.
Borisova
T A
TA
Krysanova
N V
NV
Himmelreich
N H
NH
D027322:Amino Acid Transport System X-AG / Q000037:antagonists & inhibitors*; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D001692:Biological Transport; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism*; D018471:Hypergravity; D008297:Male; D015394:Molecular Structure; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000209:etiology / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
D027322:Amino Acid Transport System X-AG; D018377:Neurotransmitter Agents; C120673:benzyloxyaspartate; C011274:3-hydroxyaspartic acid; D001224:Aspartic Acid; D018698:Glutamic Acid