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Titolo:
Antagonist effects on human P2X(7) receptor-mediated cellular accumulationof YO-PRO-1
Autore:
Michel, AD; Kaur, R; Chessell, IP; Humphrey, PPA;
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:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 3, volume: 130, anno: 2000,
pagine: 513 - 520
SICI:
0007-1188(200006)130:3<513:AEOHPR>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
ATP; MACROPHAGES; SELECTIVITY; CHANNELS;
Keywords:
P2X(7) receptor; KN62; YO-PRO-1; PPADS; oxidized ATP;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
20
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. Michel et al., "Antagonist effects on human P2X(7) receptor-mediated cellular accumulationof YO-PRO-1", BR J PHARM, 130(3), 2000, pp. 513-520

Abstract

1 We have examined the interaction of P2 antagonists with the human P2X(7)receptor by studying their effect on 2' and 3'-O-benzoyl-benzoyl-ATP (DbATP) stimulated cellular accumulation of the fluorescent, DNA binding dye, YO-PRO-1 (MW = 375Da).2 In suspensions of HEK293 cells expressing human recombinant P2X(7) receptors, DbATP produced time and concentration-dependent increases in YO-PRO-1fluorescence. This response presumably reflects YO-PRO-1 entry through P2X(7) receptor channels and binding to nucleic acids. When studies were performed in a NaCl-free, sucrose-containing buffer, full concentration-effect curves to DbATP could be constructed.3 The P2 antagonists, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) and periodate oxidized ATP (oATP), reduced the potency of DbATP and decreased its maximum response. 1-[N,O-bis(1,5-isoquinolinesulphonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN62) and its analogue, KN04, reducedthe potency of DbATP. Schild slopes for KN62 and KN04 were shallow and exhibited a plateau at concentrations of compound greater than 1 mu M, indicating that these compounds were not competitive antagonists.4 Callmidazolium and a monoclonal antibody to human P2X(7) receptors attenuated DbATP-stimulated YO-PRO-1 accumulation but they were not competitive antagonists and only produced 2-3 fold decreases in the potency of DbATP.5 The effects of PPADS and KN62 were partially reversible whereas those ofoATP were not. PPADS protected cells against the irreversible antagonist effects of oATP suggesting a common site of action. In contrast KN62 was noteffective suggesting that it may bind at a different site to oATP and PPADS.6 This study has demonstrated that P2X(7) receptor function can be quantified by measuring DbATP stimulated YO-PRO-1 accumulation and has provided additional information about the interaction of P2 receptor antagonists with the human P2X(7) receptor.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/12/20 alle ore 05:23:14