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Titolo:
Binding of an AMPA receptor potentiator ([H-3]LY395153) to native and recombinant AMPA receptors
Autore:
Linden, AM; Yu, H; Zarrinmayeh, H; Wheeler, WJ; Skolnick, P;
Indirizzi:
Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA Lilly Corp CtrIndianapolis IN USA 46285 Labs, Indianapolis, IN 46285 USA Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA Indiana Univ Indianapolis IN USA 46202 oxicol, Indianapolis, IN 46202 USA Univ Kuopio, AI Virtanen Inst, Kuopio 7021, Finland Univ Kuopio Kuopio Finland 7021 , AI Virtanen Inst, Kuopio 7021, Finland
Titolo Testata:
NEUROPHARMACOLOGY
fascicolo: 8, volume: 40, anno: 2001,
pagine: 1010 - 1018
SICI:
0028-3908(200106)40:8<1010:BOAARP>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
SELECTIVE GLUTAMATE RECEPTORS; KAINATE RECEPTORS; RAT-BRAIN; ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLE PROPIONATE; PHARMACOLOGICAL CHARACTERIZATION; ALLOSTERIC REGULATION; CHANNEL PROPERTIES; HIGH-AFFINITY; CYCLOTHIAZIDE; EXPRESSION;
Keywords:
AMPA receptors; LY395153; cyclothiazide; L-glutamate; thiocyanate; CX 516;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Skolnick, P DOV Pharmaceut, 433 Hackensack Ave, Hackensack, NJ 07601 USA DOV Pharmaceut 433 Hackensack Ave Hackensack NJ USA 07601 USA
Citazione:
A.M. Linden et al., "Binding of an AMPA receptor potentiator ([H-3]LY395153) to native and recombinant AMPA receptors", NEUROPHARM, 40(8), 2001, pp. 1010-1018

Abstract

LY395153 is a member of a newly described class of arylpropylsulfonamide AMPA receptor potentiators. Here, we characterize and compare [H-3]LY395153 binding to native AMPA receptors from rat cerebral cortex and recombinant human GluR4(flip) receptors expressed in HEK293 cells. L-Glutamate: and AMPAincreased [H-3]LY395153 binding to both native and recombinant AMPA receptors in a concentration dependent and stereoselective manner; this effect ofAMPA receptor agonists reflects an apparent increase in ligand affinity. In the presence of L-glutamate (500 muM), [H-3]LY395153 binding is saturable; the affinity of this radioligand is slightly, albeit statistically significantly higher at human GluR4(flip) (K-d=55.6 +/-5.3nM) than rat cortical receptors (K-d=110 +/- 15.1nM). NBQX competitively inhibited L-glutamate-induced increases in [H-3]LY395153 binding in both native and recombinant receptors, whilst LY303070 (the active isomer of GYKI53655) noncompetitively inhibited this effect in native, but not recombinant receptors. The prototypic AMPA receptor potentiator cyclothiazide competitively inhibited [H-3]LY395153 binding with a potency (K(i)similar to7 muM) comparable to EC,, valuesreported in electrophysiological studies. In contrast, the structurally unrelated AMPA receptor potentiator CX 516 did not inhibit [H-3]LY395153 binding at concentrations of up to 600 muM. Further, at concentrations reportedto facilitate AMPA receptor desensitization, thiocyanate acts as a competitive inhibitor of [H-3]LY395153 binding. [H-3]LY395153 binding was unaffected by a variety of structurally land mechanistically) diverse compounds tested at a concentration of 10 muM. These data indicate [H-3]LY395153 is a useful probe for labeling a unique modulatory site on both native and recombinant AMPA receptors. (C) 2001 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/07/20 alle ore 01:35:54