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Titolo:
PHARMACOLOGICAL CHARACTERIZATION OF THE HUMAN IONOTROPIC GLUTAMATE-RECEPTOR SUBTYPE GLUR3 STABLY EXPRESSED IN MAMMALIAN-CELLS
Autore:
VARNEY MA; RAO SP; JACHEC C; DEAL C; HESS SD; DAGGETT LP; LIN FF; JOHNSON EC; VELICELEBI G;
Indirizzi:
SIBIA NEUROSCI INC,505 COAST BLVD S LA JOLLA CA 92037
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 1, volume: 285, anno: 1998,
pagine: 358 - 370
SICI:
0022-3565(1998)285:1<358:PCOTHI>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT-BRAIN MEMBRANES; KAINATE RECEPTORS; AMPA RECEPTORS; ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLE PROPIONATE; CHROMOSOMAL LOCALIZATION; FUNCTIONAL EXPRESSION; QUISQUALATE RECEPTORS; SUBUNIT COMPOSITION; MOLECULAR-CLONING; CULTURED NEURONS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
74
Recensione:
Indirizzi per estratti:
Citazione:
M.A. Varney et al., "PHARMACOLOGICAL CHARACTERIZATION OF THE HUMAN IONOTROPIC GLUTAMATE-RECEPTOR SUBTYPE GLUR3 STABLY EXPRESSED IN MAMMALIAN-CELLS", The Journal of pharmacology and experimental therapeutics, 285(1), 1998, pp. 358-370

Abstract

We have cloned the human ionotropic lpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR3 flip splice variant (hGluR3(i)) and developed a stable cell line expressing this receptor in HEK293 cells. Electrophysiological recordings demonstrated that glutamate-evoked currents desensitize rapidly, with a mean desensitization time constant of 5.4 ms. Robust glutamate-evoked increases in intracellular Ca++ ([Ca++](i)) were observed in the presence of cyclothiazide, which attenuated receptor desensitization. [Ca++](i) measurements were used to perform a detailed pharmacological characterization of hGluR3(i) with reference agonists and antagonists. The results of these studies showed that kainate and domoate were not fully efficacious agonists relative to glutamate. The binding affinities of agonists and competitive antagonists were determined in a [H-3]AMPA competition binding assay. There was a good correlation between the functional data and the binding affinities obtained for competitive antagonists. However, the binding affinities of the agonists did not correlate with their functional EC50 values from [Ca++], data, possibly because the binding assay predominantly measures the desensitized high-affinity state of the receptor. [H-3]AMPA binding also was performed on membranes prepared fromrat forebrain, and comparison of the data from HEK293 cells expressing hGluR3(i) and rat forebrain suggest that nearly all of the referencecompounds show similar binding activities between the two membrane preparations, with the exception of fluoro-willardiine, kainate and 6-nitro-7-sulfamoylbenzo(f)quinoxaline-2-3-dione (NBQX). These data suggest that cells stably expressing recombinant hGluR3(i) represent pharmacologically valid experimental systems to study human AMPA receptors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/09/20 alle ore 06:29:35