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Titolo:
Ionic effects on human recombinant P2X(7) receptor function
Autore:
Michel, AD; Chessell, IP; Humphrey, PPA;
Indirizzi:
UnivJ,ambridge, Dept Pharmacol, Glaxo Inst Appl Pharmacol, Cambridge CB2 1Q Univ Cambridge Cambridge England CB2 1QJ ppl Pharmacol, Cambridge CB2 1Q
Titolo Testata:
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
fascicolo: 2, volume: 359, anno: 1999,
pagine: 102 - 109
SICI:
0028-1298(199902)359:2<102:IEOHRP>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT MAST-CELLS; EXTRACELLULAR ATP; NG108-15 CELLS; HUMAN-LYMPHOCYTES; CALCIUM INFLUX; EXTERNAL ATP; INHIBITION; PURINOCEPTOR; PERMEABILITY; MACROPHAGES;
Keywords:
P2X(7) receptor; cations; anions; YO-PRO-1; dibenzoyl-ATP;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Michel, AD Univ Cambridge, Dept Pharmacol, Glaxo Inst Appl Pharmacol, Tennis Court Rd, Univ Cambridge Tennis Court Rd Cambridge England CB2 1QJ t Rd,
Citazione:
A.D. Michel et al., "Ionic effects on human recombinant P2X(7) receptor function", N-S ARCH PH, 359(2), 1999, pp. 102-109

Abstract

The actions of monovalent and divalent ions on the P2X(7) receptor have been assessed by measuring their effect on responses to the P2 receptor agonist, 2'- and 3'-O-(4-benzoyl-benzoyl)-ATP (DbATP), in HEK293 cells expressing the human recombinant P2X(7) receptor. Tn these cells, DbATP increased the cellular accumulation of the DNA binding, fluorescent dye, YO-PRO-1. The potency of DbATP to elicit this effect was decreased by both calcium and magnesium ions. In addition, when the pH was increased above 8 or reduced below 6.5, the potency of DbATP was less than obtained at pH 7.5. Monovalent ions also affected the P2X(7) receptor such that the potency of DbATP was 19-fold higher in NaCl-free buffer containing 280 mM sucrose (pEC(50)=6.48) than in 140 mM NaCl containing buffer (pEC(50)=5.19). Monovalent cations differentially affected the potency of DbATP. Thus, when the chloride concentration was maintained at 140 mM, PEC50 values for DbATP were 6.14, 5.87 and 5.19 when the counter cation was 140 mM choline, potassium or sodium, respectively. Monovalent anions also differentially affected the potency of DbATP and in the presence of 140 mM sodium ions, PEC50 values for DbATP were 6.14, 6.07, 5.19 and 4.53, respectively, when the counter anion was 140 mM aspartate, glutamate, chloride or iodide. The inhibitory effect of monovalentanions on P2X(7) receptor function was also observed in electrophysiological studies. Thus in sodium glutamate containing buffer the potency of DbATP(pEC(50)=5.55) was approximately 22-fold higher than in NaCl containing buffer (pEC(50)=4.20). This study has demonstrated that P2X(7) receptor function can be markedly affected by a wide range of ions and that physiological concentrations of sodium and chloride ions, as well as divalent cations, contribute to the lowpotency of ATP as an agonist at this receptor.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 06:54:28