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Titolo:
Competitive antagonism of recombinant P2X(2/3) receptors by 2 ',3 '-O-(2,4,6-trinitrophenyl) adenosine 5 '-triphosphate (TNP-ATP)
Autore:
Burgard, EC; Niforatos, W; Van Biesen, T; Lynch, KJ; Kage, KL; Touma, E; Kowaluk, EA; Jarvis, MF;
Indirizzi:
Abbott Labs, Dept 4PM, Div Pharmaceut Prod, Abbott Pk, IL 60064 USA AbbottLabs Abbott Pk IL USA 60064 armaceut Prod, Abbott Pk, IL 60064 USA
Titolo Testata:
MOLECULAR PHARMACOLOGY
fascicolo: 6, volume: 58, anno: 2000,
pagine: 1502 - 1510
SICI:
0026-895X(200012)58:6<1502:CAORPR>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
SINGLE-CHANNEL PROPERTIES; GATED ION-CHANNEL; SENSORY NEURONS; HIPPOCAMPAL-NEURONS; GANGLION NEURONS; P2X RECEPTORS; RAT; CURRENTS; BLOCKADE; SUBTYPES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Burgard, EC Abbott Labs, Dept 4PM, Div Pharmaceut Prod, Bldg AP9A, Abbott Pk, IL 60064USA Abbott Labs Bldg AP9A Abbott Pk IL USA 60064 t Pk, IL 60064USA
Citazione:
E.C. Burgard et al., "Competitive antagonism of recombinant P2X(2/3) receptors by 2 ',3 '-O-(2,4,6-trinitrophenyl) adenosine 5 '-triphosphate (TNP-ATP)", MOLEC PHARM, 58(6), 2000, pp. 1502-1510

Abstract

TNP-ATP has become widely recognized as a potent and selective P2X receptor antagonist, and is currently being used to discriminate between subtypes of P2X receptors in a variety of tissues. We have investigated the ability of TNP-ATP to inhibit alpha,beta -methylene ATP (alpha,beta -meATP)-evoked responses in 1321N1 human astrocytoma cells expressing recombinant rat or human P2X(2/3) receptors. Pharmacological responses were measured using electrophysiological and calcium imaging techniques. TNP-ATP was a potent inhibitor of P2X(2/3) receptors, blocking both rat and human receptors with IC50values of 3 to 6 nM. In competition studies, 10 to 1000 muM alpha,beta -meATP was able to overcome TNP-ATP inhibition. Schild analysis revealed that TNP-ATP was a competitive antagonist with pA(2) values of -8.7 and 28.2. Inhibition of P2X(2/3) receptors by TNP-ATP was rapid in onset, reversible, and did not display use dependence. Although the onset kinetics of inhibition were concentration-dependent, the TNP-ATP off-kinetics were concentration-independent and relatively slow. Full recovery from TNP-ATP inhibition didnot occur until greater than or equal to5 s after removal of the antagonist. Because of the slow off-kinetics of TNP-ATP, full competition with alpha,beta -meATP for receptor occupancy could be seen only after both ligands had reached a steady-state condition. It is proposed that the slowly desensitizing P2X(2/3) receptor allowed this competitive interaction to be observed over time, whereas the rapid desensitization of other P2X receptors (P2X(3)) may mask the detection of competitive inhibition by TNP-ATP.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 06:25:46