 |
| Research article summary (published 30 Aug 2002): |
Characterization of the interaction between a novel convulsant agent, norbiphen, and GABA(A) and other ligand-gated ion channels.
Full Abstract
A hybrid molecule composed of the antimicrobial, norfloxacin, linked to the non-steroidal anti-inflammatory drug (NSAID), biphenylacetic acid, which we have termed norbiphen, is a lethal convulsant in vivo and an antagonist of rodent GABA(A) receptors in vitro. In the present study, the selectivity, molecular site(s) and mechanism of action of this novel convulsant were investigated using electrophysiological techniques. Sub-maximal GABA-evoked currents recorded from rodent hippocampal neurons were reversibly inhibited by norbiphen (1 microM) to 5+/-2% of control whereas glutamate, NMDA and glycine activated responses were little or unaffected. Sub-maximal GABA-evoked currents recorded from oocytes expressing recombinant human alpha1beta2gamma2s or alpha1beta2 GABA(A) receptors were also reversibly inhibited by norbiphen (1-1000 nM) with an IC(50) (+/-s.e.m.) of 5.7+/-1 and 8.8+/-1 nM, respectively. Similarly, GABA currents recorded from alpha1beta1gamma2s, alpha1beta1 and beta2gamma2s receptors were inhibited with IC(50)s of 16.1+/-1, 18.8+/-1 and 4.2+/-1 nM, respectively. In contrast, norbiphen (100 nM) had little or no effect at rho1 GABA(C) homomers. At alpha1beta2gamma2s receptors, norbiphen had no affect on the GABA reversal potential, and inhibition was not voltage-dependent, suggesting that this compound does not act at the ion channel. The GABA concentration response curve was shifted in a competitive-like fashion by norbiphen (10-300 nM) and a Schild analysis of these data yielded a slope of 0.94+/-0.1 and a pA(2) of 7.77. Our data reveal a novel, selective and highly potent antagonist of GABA(A) receptors. Norbiphen should be a valuable agent in future studies of this receptor complex.
Learn Faster Today Improve your study skills
Author information
Author/s: Halliwell, R F (RF); Su, Jiping (J); Demuro, A (A); Martinez-Torres, A (A); Miledi, R (R);
Affiliation: School of Biological & Biomedical Sciences, University of Durham, UK. rhalliwell(-atsign-)uop.edu
Journal and publication information
Publication Type: Journal Article; Research Support, Non-U.S. Gov't
Journal: Neuropharmacology (Neuropharmacology), published in England. (Language: eng)
Reference: 2002-Sep; vol 43 (issue 4) : pp 778-87
Dates: Created 2002/10/07; Completed 2002/12/24; Revised 2006/11/15;
PMID: 12367622, status: MEDLINE (last retrieval date: 11/6/2008)
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
External Links for this article (including full text providers, if available):
Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.
This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.
MeSH headings (categories)
This article was linked to the MESH Headings shown below.
|
|
Related articles
This article has not been indexed for related articles as yet, however you can still use the live related article search links below.
See a large map of 100+ related articles.