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

Abstract

The effects of highly-selective blocker of γ-aminobutyric acid transporters of GAT1, NO-711, and substrate inhibitor of γ aminobutyric acid transporters GAT3, ß-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 ß-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 ß-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 ß-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, ß-alanine is a promising substance for development of neurotropic pharmacological preparations for the transporter-mediated regulation of GABA-ergic neurotransmission.

Keywords

• perinatal hypoxia
• plasma membrane GABA
• transporters
• NO-711