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Title

Effects of the conformationally restricted GABA analogues, cis-and trans-4-aminocrotonic acid, on GABA neurotransmission in primary neuronal cultures

AuthorsVale, Carmen; Vilaró, Maria Teresa ; Rodríguez-Farré, Eduard; Suñol, Cristina
KeywordsGABA receptors
Cl- flux
primary neuronal cultures
GABA uptake
RT-PCR
flunitrazepam binding
Issue Date1-Jul-1999
PublisherJohn Wiley & Sons
CitationJournal of Neuroscience Research 57(1): 95-105 (1999)
AbstractThe effects of the GABA analogues, cis- and trans-4-aminocrotonic acid (ACA) on GABA(A) receptor function and GABA uptake, together with the presence of p-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 γ- hexachlorocyclohexane (γ-HCH or lindane). [3H]-flunitrazepam binding was also increased by both isomers and this increase was inhibited by bicuculline. In neocortical neurons, the trans-isomer completely inhibited the [3H]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 p-1 subunit which assembles to form homooligomeric Cl- channels. The results presented here show that p-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.
Publisher version (URL)http://dx.doi.org/10.1002/(SICI)1097-4547(19990701)57:1<95::AID-JNR10>3.0.CO;2-N
URIhttp://hdl.handle.net/10261/113015
DOI10.1002/(SICI)1097-4547(19990701)57:1<95::AID-JNR10>3.0.CO;2-N
Identifiersdoi: 10.1002/(SICI)1097-4547(19990701)57:1<95::AID-JNR10>3.0.CO;2-N
issn: 0360-4012
Appears in Collections:(IIBB) Artículos
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