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ISSN 2410-776X (Online),
ISSN 2410-7751 (Print)

 3 2015

Biotechnologia Acta V. 8, No 3, 2015
https://doi.org/10.15407/biotech8.03.067
Р. 67-77, Bibliography 46, Ukrainian
Universal Decimal Classification: 612.822:615.853:577.352:577.122.7

THE EFFECTS OF NO-711 AND β-ALANINE ON GLUTAMATE AND γ -AMINOBUTYRIC ACID UPTAKE BY NERVE TERMINALS ISOLATED FROM RATS AFTER PERINATAL HYPOXIA

Dudarenko M. V., Yatsenko L. M., Piskova M. V., Nazarova A. G., Voronova O. O., Pastukhov A. O., Pozdnyakova N. G.

Palladin Institute of Biochemistry, of the National Academie of Sciences of Ukraine, Kyiv

The effects of highly-selective blocker of γ-aminobutyric acid transporters of GAT1, NO-711, and substrate inhibitor of γ aminobutyric acid transporters GAT3, β-alanine on the initial velocity of L-[14C]glutamate and [3H]-γ-aminobutyric acid uptake by cortical, hippocampal and thalamic nerve terminals (synaptosomes) were analyzed in norm and after perinatal hypoxia.

Rats were underwent to hypoxia and seizures (airtight chamber, 4% O2 and 96% N2) at the age of 10–12 postnatal days. The experiments were performed at 8–9 weeks in the control and after hypoxia. It was shown that NO-711 (30 microM) and β-alanine (100 microM) did not affect initial velocity of L-[14C] glutamate uptake by cortical, hippocampal and thalamic synaptosomes. In cortical synaptosomes, NO-711 and β-alanine decreased the initial velocity of [3H]-γ-aminobutyric acid uptake, but their inhibitory effects were similar in control and hypoxia groups. The effectiveness of β-alanine to influence [3H]-γ-aminobutyric acid uptake was increased in hippocampal and thalamic nerve terminals as a result of perinatal hypoxia, whereas the capacity of NO-711 in thalamic nerve terminals was decreased.

These results suggest changes in the ratio of active GAT1/GAT3 expressed in the plasma membrane of nerve terminals after perinatal hypoxia. Thus, β-alanine is a promising substance for development of neurotropic pharmacological preparations for the transporter-mediated regulation of GABA-ergic neurotransmission.

Key words: perinatal hypoxia, plasma membrane GABA transporters, NO-711, β-alanine.

© Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, 2015