Effects of the conformationally restricted GABA analogues, Cis-and Trans-4-aminocrotonic acid, on GABA neurotransmission in primary neuronal cultures
✍ Scribed by Carmen Vale; M. Teresa Vilaró; Eduardo Rodríguez-Farré; Cristina Suñol
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 217 KB
- Volume
- 57
- Category
- Article
- ISSN
- 0360-4012
No coin nor oath required. For personal study only.
✦ Synopsis
The effects of the GABA analogues, cis-and trans-4aminocrotonic acid (ACA) on GABA A receptor function and GABA uptake, together with the presence of -1 subunit mRNA and putative GABA C receptors, were studied in primary cultures of neocortical neurons and cerebellar granule cells. Both isomers induced a Cl -influx, which was inhibited by bicuculline, t-butylbicyclophosphorothionate (TBPS), picrotoxinin (PTX), and ␥-hexachlorocyclohexane (␥-HCH or lindane). [ 3 H]-flunitrazepam binding was also increased by both isomers and this increase was inhibited by bicuculline. In neocortical neurons, the transisomer completely inhibited the [ 3 H]GABA uptake, whereas the cis-isomer produced only a 25% inhibition at the highest concentration used. The possible presence of GABA C receptors was investigated only in neocortical cultures by using RT-PCR in order to detect the presence of the mRNA encoding the -1 subunit which assembles to form homooligomeric Cl - channels. The results presented here show that -1 subunits, and thus GABA C receptors, may represent a very minor population of GABA receptors in these neuronal preparations. We conclude that both GABA analogues may act as agonists at the GABA A receptors, although with very different potencies.