title: Perinatal hypoxia: different effects of the inhibitors of GABA transporters GAT1 and GAT3 on the initial velocity of [3H]GABA uptake by cortical, hippocampal, and thalamic nerve terminals.
abstract: AIM. To analyze the effects of highly selective blocker GAT1, NO-711, and substrate inhibitor GAT3, β-alanine, on the initial velocity of [(3)H]GABA uptake by cortical, hippocampal, and thalamic nerve terminals (synaptosomes) after perinatal hypoxia. METHODS. Animals were divided into two groups: control (n=17) and hypoxia (n=12). Rats in the hypoxia group underwent hypoxia and seizures (airtight chamber, 4% O2 and 96% N2) at the age of 10-12 postnatal days and were used in the experiments 8-9 weeks after hypoxia. RESULTS. In cortical synaptosomes, the effects of NO-711 (30 μΜ) and β-alanine (100 μΜ) on [(3)H]GABA uptake were similar in control and hypoxia groups. In hippocampal synaptosomes, NO-711 inhibited 84.3% of the initial velocity of [(3)H]GABA uptake in normal conditions and 80.1% after hypoxia, whereas the effect of β-alanine was increased after hypoxia from 14.4% to 22.1%. In thalamic synaptosomes, the effect of NO-711 was decreased by 79.6% in controls and by 70.9% in hypoxia group, whereas the effect of β-alanine was increased after hypoxia from 20.2% to 30.2%. CONCLUSIONS. The effectiveness of β-alanine to influence GABA uptake was increased in hippocampal and thalamic nerve terminals as a result of perinatal hypoxia and the effectiveness of NO-711 in thalamic nerve terminals was decreased. These results may indicate changes in the ratio of active GAT1/GAT3 expressed in the plasma membrane of nerve terminals after perinatal hypoxia. We showed a possibility to modulate non-GAT1 GABA transporter activity in different brain regions by exogenous and endogenous β-alanine.
authors.forename: Natalia
authors.initials: N
authors.lastname: Pozdnyakova
authors.forename: Marina
authors.initials: M
authors.lastname: Dudarenko
authors.forename: Ludmila
authors.initials: L
authors.lastname: Yatsenko
authors.forename: Nina
authors.initials: N
authors.lastname: Himmelreich
authors.forename: Olga
authors.initials: O
authors.lastname: Krupko
authors.affiliation: Tatiana Borisova, Palladin Institute of Biochemistry, NAS of Ukraine, 9 Leontovicha Street, Kiev, 01601, Ukraine, tborisov@biochem.kiev.ua.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Borisova
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D050485:GABA Plasma Membrane Transport Proteins / Q000378:metabolism*; D058805:GABA Uptake Inhibitors / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D009557:Nipecotic Acids / Q000494:pharmacology; D010091:Oximes / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D013788:Thalamus / Q000187:drug effects* / Q000378:metabolism; D015091:beta-Alanine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D050485:GABA Plasma Membrane Transport Proteins; D058805:GABA Uptake Inhibitors; D009557:Nipecotic Acids; D010091:Oximes; D015091:beta-Alanine; C078793:NNC 711; D005680:gamma-Aminobutyric Acid