Partial agonism of taurine at gamma-containing native and recombinant GABAA receptors.
PLoS One
; 8(4): e61733, 2013.
Article
em En
| MEDLINE
| ID: mdl-23637894
ABSTRACT
Taurine is a semi-essential sulfonic acid found at high concentrations in plasma and mammalian tissues which regulates osmolarity, ion channel activity and glucose homeostasis. The structural requirements of GABAA-receptors (GABAAR) gated by taurine are not yet known. We determined taurine potency and efficacy relative to GABA at different types of recombinant GABAAR occurring in central histaminergic neurons of the mouse hypothalamic tuberomamillary nucleus (TMN) which controls arousal. At binary α(1/2)ß(1/3) receptors taurine was as efficient as GABA, whereas incorporation of the γ(1/2) subunit reduced taurine efficacy to 60-90% of GABA. The mutation γ(2F77I), which abolishes zolpidem potentiation, significantly reduced taurine efficacy at recombinant and native receptors compared to the wild type controls. As taurine was a full- or super- agonist at recombinant αxß1δ-GABAAR, we generated a chimeric γ(2) subunit carrying the δ subunit motif around F77 (MTVFLH). At α(1/2)ß(1)γ2(MTVFLH) receptors taurine became a super-agonist, similar to δ-containing ternary receptors, but remained a partial agonist at ß3-containing receptors. In conclusion, using site-directed mutagenesis we found structural determinants of taurine's partial agonism at γ-containing GABAA receptors. Our study sheds new light on the ß1 subunit conferring the widest range of taurine-efficacies modifying GABAAR function under (patho)physiological conditions.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Taurina
/
Receptores de GABA-A
/
Agonistas de Receptores de GABA-A
Limite:
Animals
Idioma:
En
Revista:
PLoS One
Ano de publicação:
2013
Tipo de documento:
Article