Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
PROPERTIES OF THE PORE-FORMING P2X(7) PURINOCEPTOR IN MOUSE NTW8 MICROGLIAL CELLS
Autore:
CHESSELL IP; MICHEL AD; HUMPHREY PPA;
Indirizzi:
UNIV CAMBRIDGE,DEPT PHARMACOL,GLAXO INST APPL PHARMACOL,TENNIS COURT RD CAMBRIDGE CB2 1QJ ENGLAND
Titolo Testata:
British Journal of Pharmacology
fascicolo: 7, volume: 121, anno: 1997,
pagine: 1429 - 1437
SICI:
0007-1188(1997)121:7<1429:POTPPP>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
CENTRAL-NERVOUS-SYSTEM; ADENOSINE-TRIPHOSPHATE; PURINERGIC RECEPTORS; ALZHEIMERS-DISEASE; PATCH-CLAMP; MAST-CELLS; ATP; MEMBRANE; RELEASE;
Keywords:
MICROGLIA; P2X(7) PURINOCEPTOR; PORE; ETHIDIUM BROMIDE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
31
Recensione:
Indirizzi per estratti:
Citazione:
I.P. Chessell et al., "PROPERTIES OF THE PORE-FORMING P2X(7) PURINOCEPTOR IN MOUSE NTW8 MICROGLIAL CELLS", British Journal of Pharmacology, 121(7), 1997, pp. 1429-1437

Abstract

1 We have used whole-cell patch clamping methods to study and characterize the cytolytic P2X, (P2Z) receptor in the NTW8 mouse microglial cell line. 2 At room temperature, in an extracellular solution containing 2 mM Ca2+ and 1 mM Mg2+, 2'- and 3'-O-(4-benzoylbenzoyl)-adenosine-5'-triphosphate (Bz-ATP; 300 mu M), or ATP (3 mM), evoked peak whole cell inward currents, at a holding potential of -90 mV, of 549 +/- 191 and 644 +/- 198 pA, respectively. Current-voltage relationships generated with 3 mM ATP reversed at 4.6 mV and did not display strong rectification. 3 In an extracellular solution containing zero Mg2+ and 500 mu M Ca2+ (low divalent solution), brief (0.5 s) application of these agonists elicited larger maximal currents (909 +/- 138 and 1818 +/- 218pA, Bz-ATP and ATP, respectively). Longer application of ATP (1 mM for 30 s) produced larger, slowly developing, currents which reached a plateau after approximately 15-20 s and were reversible on washing. Under these conditions, in the presence of ATP, ethidium bromide uptake could be demonstrated. Further applictions of 1 mM ATP produced rapid currents of the same magnitude as those observed during the 30 s application. Subsequent determination of concentration-effect curves to Bz-ATP, ATP and 2-methylthio-ATP yielded EC50 values of 58.3, 298 and 505 mu M, respectively. These affects of ATP were antagonized by pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 30 mu M) but notsuramin (100 mu M). 4 In low divalent solution, repeated application of 1 mM ATP for is produced successively larger currents which reacheda plateau, after 8 applications, of 466% of the first application current. PPADS (30 mu M) prevented this augmentation, while 5-(N,N-hexamethylene)-amiloride (HMA) (100 mu M) accelerated it such that maximal augmentation was observed after only one application of ATP in the presence of HMA. At a bath temperature of 32 degrees C, current augmentation also occurred in normal divalent cation containing solution. 5 These data demonstrate that mouse microglial NTW8 cells possess a purinoceptor with pharmacological characteristics resembling the P2X receptor. We suggest that the current augmentation phenomenon observed reflectsformation of the la:ge cytolytic pore characteristic of this receptor. We have demonstrated that pore formation can occur under normal physiological conditions and can be modulated pharmacologically, both positively and negatively.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 07:02:37