Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Differential cross talk of ROD compounds with the benzodiazepine binding site
Autore:
Sigel, E; Baur, R; Furtmueller, R; Razet, R; Dodd, RH; Sieghart, W;
Indirizzi:
Univ Bern, Dept Pharmacol, CH-3010 Bern, Switzerland Univ Bern Bern Switzerland CH-3010 Pharmacol, CH-3010 Bern, Switzerland Univ Vienna, Brain Res Inst, Sect Biochem & Mol Biol, Vienna, Austria UnivVienna Vienna Austria st, Sect Biochem & Mol Biol, Vienna, Austria CNRS, Inst Chim Subst Nat, Gif Sur Yvette, France CNRS Gif Sur Yvette France Inst Chim Subst Nat, Gif Sur Yvette, France
Titolo Testata:
MOLECULAR PHARMACOLOGY
fascicolo: 6, volume: 59, anno: 2001,
pagine: 1470 - 1477
SICI:
0026-895X(200106)59:6<1470:DCTORC>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
GABA-A-RECEPTOR; ALLOSTERIC MODULATION; XENOPUS OOCYTES; SUBUNIT; PHARMACOLOGY; LIGANDS; SUBTYPES; ACID; BICUCULLINE; EXPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
22
Recensione:
Indirizzi per estratti:
Indirizzo: Sigel, E Univ Bern, Dept Pharmacol, CH-3010 Bern, Switzerland Univ Bern Bern Switzerland CH-3010 l, CH-3010 Bern, Switzerland
Citazione:
E. Sigel et al., "Differential cross talk of ROD compounds with the benzodiazepine binding site", MOLEC PHARM, 59(6), 2001, pp. 1470-1477

Abstract

We have recently identified a novel class of allosteric modulators of GABA(A) receptors, the ROD compounds that are structurally related to bicuculline. Here, the relationship of their site of action relative to other known modulatory sites of this receptor was investigated. Two types of ROD compounds, R1 (ROD164A, ROD185) and R2 (ROD222 and ROD259) could be differentiated. R1 compounds competitively inhibited binding of benzodiazepines in alpha1 beta2 gamma2 receptors, and their functional effects were partially inhibited by the benzodiazepine antagonist Ro15-1788 in a noncompetitive manner. The enhancement by an R1 compound was not additive with that by diazepam. R2 compounds in contrast failed to inhibit binding of benzodiazepines; the R2 compounds' functional effects were not inhibited by the benzodiazepine antagonist. The enhancement by an R2 compound was additive with that by diazepam. In contrast to benzodiazepines, both R1 and R2 type compounds were still able to enhance alpha1 beta2 receptors. ROD164A in alpha1 beta2 gamma2 receptors was found to be partially antagonized by Ro15-1788 in a noncompetitive way. ROD178B did not affect gamma -aminobutyric acid induced currents, but was able to inhibit both enhancement by R1 and R2 type compounds as well as enhancement by diazepam. R1 and R2 type compounds as well as diazepam enhanced pentobarbital-induced currents in a Ro15-1788-sensitive way. We conclude that R1 type compounds act at the benzodiazepine binding site and additionally at a different R1 site, and that the R1, but not the R2 site is allosterically coupled to the benzodiazepine binding site. ROD178B is a competitive antagonist at the R1 site in that it shows allosteric interaction with the benzodiazepine binding site and displacement of benzodiazepines,and a negative allosteric modulator at the R2 site.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/07/20 alle ore 12:17:03