Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Characterization of the binding site for a novel class of noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonists
Autore:
Menniti, FS; Chenard, BL; Collins, MB; Ducat, MF; Elliott, ML; Ewing, FE; Huang, JI; Kelly, KA; Lazzaro, JT; Pagnozzi, MJ; Weeks, JL; Welch, WM; White, WF;
Indirizzi:
Pfizer Inc, Global Res & Dev, Groton, CT 06340 USA Pfizer Inc Groton CT USA 06340 nc, Global Res & Dev, Groton, CT 06340 USA
Titolo Testata:
MOLECULAR PHARMACOLOGY
fascicolo: 6, volume: 58, anno: 2000,
pagine: 1310 - 1317
SICI:
0026-895X(200012)58:6<1310:COTBSF>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
NON-NMDA RECEPTOR; AMPA RECEPTORS; GLUTAMATE RECEPTORS; PREFERRING RECEPTORS; KAINATE-RECEPTORS; FOCAL ISCHEMIA; GYKI 52466; RAT; MODULATION; NBQX;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Menniti, FS Pfizer Inc, Global Res & Dev, Eastern Point Rd, Groton, CT 06340 USA Pfizer Inc Eastern Point Rd Groton CT USA 06340 , CT 06340 USA
Citazione:
F.S. Menniti et al., "Characterization of the binding site for a novel class of noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonists", MOLEC PHARM, 58(6), 2000, pp. 1310-1317

Abstract

The alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor is an ionotropic glutamate receptor that mediates fast excitatory synaptic transmission throughout the central nervous system. In addition to the glutamate binding site, allosteric modulatory sites on the receptor are inferred from the ability of synthetic compounds to affect channel function without interaction with the glutamate binding site. We have identified a novel class of potent, noncompetitive AMPA receptor antagonists typified by CP-465,022 and CP-526,427. The latter compound was radiolabeled and used to elucidate the pharmacology of one allosteric modulatory site. [H-3] CP-526,427 labels a single binding site in rat forebrain membranes with a K-d valueof 3.3 nM and a B-max of 7.0 pmol/mg of protein. The [H-3] CP-526,427 binding site does not seem to interact directly with the glutamate binding sitebut overlaps with that for another class of AMPA receptor antagonists, the2,3-benzodiazepines. This binding site is distinct from that for the antagonist Evans blue and for several classes of compounds that modulate AMPA receptor desensitization. These results indicate the existence of at least two physically distinct allosteric sites on the AMPA receptor through which channel activity or desensitization is modulated.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 06:52:35