Original scientific paper
https://doi.org/10.3325/cmj.2014.55.250
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
Natalia Pozdnyakova
; Department of Neurochemistry Palladin Institute of Biochemistry National Academy of Sciences of Ukraine, Kiev, Ukraine
Marina Dudarenko
; Department of Neurochemistry Palladin Institute of Biochemistry National Academy of Sciences of Ukraine, Kiev, Ukraine
Ludmila Yatsenko
; Department of Neurochemistry Palladin Institute of Biochemistry National Academy of Sciences of Ukraine, Kiev, Ukraine
Nina Himmelreich
; Department of Neurochemistry Palladin Institute of Biochemistry National Academy of Sciences of Ukraine, Kiev, Ukraine
Olga Krupko
; Department of Neurochemistry Palladin Institute of Biochemistry National Academy of Sciences of Ukraine, Kiev, Ukraine
Tatiana Borisova
; Department of Neurochemistry Palladin Institute of Biochemistry National Academy of Sciences of Ukraine, Kiev, Ukraine
Abstract
Aim To analyze the effects of highly selective blocker GAT1,
NO-711, and substrate inhibitor GAT3, β-alanine, on the initial
velocity of [3H]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 [3H]GABA uptake were
similar in control and hypoxia groups. In hippocampal synaptosomes,
NO-711 inhibited 84.3% of the initial velocity
of [3H]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
Keywords
Hrčak ID:
129841
URI
Publication date:
15.6.2014.
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