Literature DB >> 8161449

A novel allosteric modulatory site on the GABAA receptor beta subunit.

K A Wafford1, C J Bain, K Quirk, R M McKernan, P B Wingrove, P J Whiting, J A Kemp.   

Abstract

Cloning of cDNAs that code for GABAA receptor subunits has revealed multiple receptor populations constructed from different subunit combinations. On native rat and cloned human GABAA receptors, the anticonvulsant compound loreclezole strongly potentiated GABA-mediated chloride currents. Using different combinations of human GABAA receptor subunits expressed in Xenopus oocytes and transfected 293 cells, loreclezole was highly selective for receptors containing the beta 2 or beta 3 subunit over those containing the beta 1 subunit. Loreclezole was demonstrated to act at a site distinct from the benzodiazepine, barbiturate, and steroid sites with a unique subunit dependence. These results describe a previously unidentified modulatory site on the GABAA receptor beta subunit that allows pharmacological discrimination of different GABAA receptor subpopulations in the brain and provides a new target for putative anticonvulsant/anxiolytic drugs.

Entities:  

Mesh：

Substances：

Year:  1994        PMID： 8161449     DOI： 10.1016/0896-6273(94)90330-1

Source DB:  PubMed          Journal:  Neuron        ISSN： 0896-6273            Impact factor:   17.173


  46 in total

1.  Dual mode of stimulation by the beta-carboline ZK 91085 of recombinant GABA(A) receptor currents: molecular determinants affecting its action.

Authors:  U Thomet; R Baur; P Scholze; W Sieghart; E Sigel
Journal:  Br J Pharmacol       Date:  1999-07       Impact factor: 8.739

2.  Composition of the GABA(A) receptors of retinal dopaminergic neurons.

Authors:  S Gustincich; A Feigenspan; W Sieghart; E Raviola
Journal:  J Neurosci       Date:  1999-09-15       Impact factor: 6.167

3.  Allosteric modulators affect the efficacy of partial agonists for recombinant GABA(A) receptors.

Authors:  G Maksay; S A Thompson; K A Wafford
Journal:  Br J Pharmacol       Date:  2000-04       Impact factor: 8.739

4.  Do antiepileptics phenytoin, carbamazepine, and loreclezole show GABA(A) receptor subtype selectivity in rat brain sections?

Authors:  I E Holopainen; R Kivelä; E R Korpi
Journal:  Neurochem Res       Date:  2001-01       Impact factor: 3.996

5.  Major differences in inhibitory synaptic transmission onto two neocortical interneuron subclasses.

Authors:  Alberto Bacci; Uwe Rudolph; John R Huguenard; David A Prince
Journal:  J Neurosci       Date:  2003-10-22       Impact factor: 6.167

6.  Fast IPSCs in rat thalamic reticular nucleus require the GABAA receptor beta1 subunit.

Authors:  Molly M Huntsman; John R Huguenard
Journal:  J Physiol       Date:  2006-02-09       Impact factor: 5.182

7.  A gain in GABAA receptor synaptic strength in thalamus reduces oscillatory activity and absence seizures.

Authors:  Claude M Schofield; Max Kleiman-Weiner; Uwe Rudolph; John R Huguenard
Journal:  Proc Natl Acad Sci U S A       Date:  2009-04-20       Impact factor: 11.205

8.  Hearing loss alters the subcellular distribution of presynaptic GAD and postsynaptic GABAA receptors in the auditory cortex.

Authors:  Emma C Sarro; Vibhakar C Kotak; Dan H Sanes; Chiye Aoki
Journal:  Cereb Cortex       Date:  2008-04-09       Impact factor: 5.357

9.  Mutation at the putative GABA(A) ion-channel gate reveals changes in allosteric modulation.

Authors:  S A Thompson; M Z Smith; P B Wingrove; P J Whiting; K A Wafford
Journal:  Br J Pharmacol       Date:  1999-07       Impact factor: 8.739

Review 10.  The diversity of GABAA receptors. Pharmacological and electrophysiological properties of GABAA channel subtypes.

Authors:  W Hevers; H Lüddens
Journal:  Mol Neurobiol       Date:  1998-08       Impact factor: 5.590
View more

北京卡尤迪生物科技股份有限公司 © 2022-2023.