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Titolo:
Species- and agonist-dependent differences in the deactivation-kinetics ofP2X(7) receptors
Autore:
Hibell, AD; Thompson, KM; Simon, J; Xing, M; Humphrey, PPA; Michel, AD;
Indirizzi:
Univ Cambridge, Dept Pharmacol, Glaxo Inst Appl Pharmacol, Cambridge CB2 1QJ, England Univ Cambridge Cambridge England CB2 1QJ col, Cambridge CB2 1QJ, England
Titolo Testata:
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
fascicolo: 6, volume: 363, anno: 2001,
pagine: 639 - 648
SICI:
0028-1298(200106)363:6<639:SAADIT>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACETYLCHOLINE-RECEPTORS; CATION CHANNELS; XENOPUS-OOCYTES; NMDA RECEPTORS; PATCH-CLAMP; PORE; CELLS; AFFINITY; NEURONS; PURINOCEPTOR;
Keywords:
BzATP; P2X(7) receptor; ion-channel;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Michel, AD Univ Cambridge, Dept Pharmacol, Glaxo Inst Appl Pharmacol, Tennis Court Rd, Cambridge CB2 1QJ, England Univ Cambridge Tennis Court Rd Cambridge England CB2 1QJ gland
Citazione:
A.D. Hibell et al., "Species- and agonist-dependent differences in the deactivation-kinetics ofP2X(7) receptors", N-S ARCH PH, 363(6), 2001, pp. 639-648

Abstract

In this study we have expressed recombinant P2X(7) receptors in HEK293 cells and examined the reasons for the species- and agonist-dependent differences in the time taken for the closure of the P2X(7) receptor ion-channels after agonist removal. Channel closure times, measured in electrophysiological studies or by measuring cellular permeability to ethidium cations, were slower at rat than athuman or mouse P2X(7) channels following washout of the P2X(7) agonist 2'-and 3'-O-(4-benzoylbenzoyl)-ATP (BzATP). In contrast, there were no species differences in channel closure times when ATP was the agonist. BzATP was more potent than ATP at the three species homologues and exhibited highest potency for rat P2X(7) receptors suggesting that channel closure time was related to agonist potency. Furthermore, BzATP potency for the P2X(7) receptor could be modified by changing extracellular ionic concentrations or by mutating the receptor and modifications which increased agonist potency alsoincreased the time taken for channel closure. The dependence of channel closure time on agonist potency suggests it reflects agonist dissociation from the P2X(7) receptor rather being an intrinsic property of the ion-channel. Consistent with this, our previous studies have shown that agonist potency increases after repeated agonist applications and in this study channel closure time at rat P2X(7) receptors increased after repeated agonist applications. Overall these results suggest that thespecies differences in channel closure times reflect differences in agonist dissociation rates which arise as a consequence of the marked species differences in agonist potency.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/11/20 alle ore 14:18:37