The ATP4− receptor-operated ion channel of human lymphocytes: Inhibition of ion fluxes by amiloride analogs and by extracellular sodium ions

Wiley, James S.; Chen, Rong; Wiley, Malcolm J.; Jamieson, Gary P.

doi:10.1016/0003-9861(92)90010-t

Cited by 80 publications

(82 citation statements)

References 47 publications

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“…phocytes is the inhibition of ion fluxes which is observed at high extracellular Na' concentrations ( Figure la). A similar inhibitory action of extracellular Na' on ATPinduced Ca21 transients has been reported for mouse thymocytes (Pizzo et al, 1991) and human lymphocytes but is not observed with Ca2" transients produced by agonists such as anti human immunoglobulin antibody (Wiley et al, 1992), an observation which excludes some generalized effect of extracellular Na' on Ca2' homeostasis, e.g. by Ca2+-Na' countertransport.…”

Section: Discussionsupporting

confidence: 75%

The P_2Z‐purinoceptor of human lymphocytes: actions of nucleotide agonists and irreversible inhibition by oxidized ATP

Wiley

Chen

Snook

et al. 1994

British J Pharmacology

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Extracellular adenosine triphosphate (ATP) is known to open a receptor‐operated ion channel (P2Z class) in human lymphocytes which conducts a range of cationic permeants. The activity of a range of different agonists and inhibitors towards the P2Z‐purinoceptor was investigated by measuring the agonist‐induced influx of Ba2+ into fura‐2 loaded lymphocytes. The most potent agonist was 2′ & 3′‐0‐(4‐benzoylbenzoyl)‐ATP (benzoylbenzoic ATP) which gave 2 fold greater maximum Ba2+ influx and had a 10 fold lower EC50 than for ATP. The rank order of agonist potency in K+‐media was benzoylbenzoic ATP>>ATP = 2‐methylthio ATP = 2‐chloro ATP>ATP‐γ‐S. ADP, UTP and α,β‐methylene ATP were unable to stimulate Ba2+ influx. Extracellular Na+ inhibited the increment of Ba2+ influx induced by all concentrations of ATP, 2‐methylthio ATP, 2‐chloroATP and ATP‐γ‐S. This inhibitory effect of extracellular Na+ is also reflected in the different EC50s for benzoylbenzoic ATP (8 μm in K+‐media, 18 μm in Na+‐media) but the maximal response to this agonist was the same in the presence or absence of Na+. Treatment of lymphocytes with 2,3 dialdehyde ATP (oxidized ATP) at 300 μm for 60 min gave total and irreversible inhibition of ATP‐induced Ba2+ influx. 5′‐p‐Fluorosulphonyl benzoyladenosine (FSBA) also was an irreversible inhibitor but the maximal inhibition achieved was 90%. It is concluded that the P2Z‐purinoceptor of human lymphocytes has a rank order of agonist potency which clearly distinguishes it from other P2‐receptors and that oxidized ATP is a convenient irreversible inhibitor for the P2Z‐purinoceptor.

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Section: Discussionsupporting

confidence: 75%

The P_2Z‐purinoceptor of human lymphocytes: actions of nucleotide agonists and irreversible inhibition by oxidized ATP

Wiley

Chen

Snook

et al. 1994

British J Pharmacology

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“…In contrast to these studies, we found that neither K + efflux, Na + influx, Ca 2+ influx nor an increase in intracellular Ca 2+ is essential for P2X7-induced CD23 shedding from RPMI 8226 cells. Of note, choline-Cl and KCl medium potentiated ATPinduced CD23 shedding compared to NaCl medium, which is likely due to the omission of extracellular Na + , a cation known to inhibit P2X7 activity [50,51], as well as the possible inhibition of phosphatidic acid production by choline as discussed above.…”

Section: Discussionmentioning

confidence: 89%

CAY10593 inhibits the human P2X7 receptor independently of phospholipase D1 stimulation

Pupovac

Stokes

Sluyter

2013

Purinergic Signalling

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The P2X7 receptor is a trimeric ATP-gated cation channel important in health and disease. We have observed that the specific phospholipase D (PLD)1 antagonist, CAY10593 impairs P2X7-induced shedding of the 'low affinity' IgE receptor, CD23. The current study investigated the mode of action of this compound on P2X7 activation. Measurements of ATP-induced ethidium + uptake revealed that CAY10593 impaired P2X7-induced pore formation in human RPMI 8226 B cells, P2X7-transfected HEK-293 cells and peripheral blood mononuclear cells. Concentration response curves demonstrated that CAY10593 impaired P2X7-induced pore formation in RPMI 8226 cells more potently than the PLD2 antagonist CAY10594 and the non-specific PLD antagonist halopemide. Electrophysiology measurements demonstrated that CAY10593 also inhibited P2X7-induced inward currents. Notably, RT-PCR demonstrated that PLD1 was absent in RPMI 8226 cells, while choline-Cl medium or 1-butanol, which block PLD stimulation and signalling respectively did not impair P2X7 activation in these cells. This data indicates that CAY10593 impairs human P2X7 independently of PLD1 stimulation and highlights the importance of ensuring that compounds used in signalling studies downstream of P2X7 activation do not affect the receptor itself.

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“…Canine P2X 7 is less sensitive to inhibition by extracellular Na + ions compared to human P2X 7 The relative potency of BzATP and ATP on human and rodent P2X 7 is reduced in the presence of extracellular Na + ions [21,22], however, the effect extracellular Na + ions on canine P2X 7 is unknown. Therefore, the BzATP-and ATP-induced efflux of 86 Rb + from canine and human erythrocytes in KCl medium (nominally free of Na + ions) and NaCl medium was measured (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Inhibition of P2X 7 by extracellular Na + ions is a well-described event [21,22], which is thought to occur via a regulatory Na + binding site on the extracellular loop of the receptor within the electrical field of the membrane [35]. EC 50 values for both canine and human P2X 7 to either agonist were higher in the presence of extracellular Na + .…”

Section: Discussionmentioning

confidence: 99%

The P2X7 receptor mediates the uptake of organic cations in canine erythrocytes and mononuclear leukocytes: comparison to equivalent human cell types

Stevenson

Taylor

Wiley

et al. 2009

Purinergic Signalling

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We previously demonstrated that canine erythrocytes express the P2X 7 receptor, and that the function and expression of this receptor is greatly increased compared with human erythrocytes. Using 86 Rb + (K + ) and organic cation flux measurements, we further compared P2X 7 in erythrocytes and mononuclear leukocytes from these species. Concentration response curves of BzATP-and ATP-induced 86 Rb + efflux demonstrated that canine P2X 7 was less sensitive to inhibition by extracellular Na + ions compared to human P2X 7 . In contrast, canine and human P2X 7 showed a similar sensitivity to the P2X 7 antagonists KN-62 and Mg 2+ . KN-62 and Mg 2+ also inhibited ATPinduced choline + uptake into canine and human erythrocytes. BzATP and ATP but not ADP or NAD induced ethidium + uptake into canine monocytes, T-and B-cells. ATP-induced ethidium + uptake was twofold greater in canine T-cells compared to canine B-cells and monocytes. KN-62 inhibited the ATP-induced ethidium + uptake in each cell type. P2X 7 -mediated uptake of organic cations was 40-and fivefold greater in canine erythrocytes and lymphocytes (T-and B-cells), respectively, compared to equivalent human cell types. In contrast, P2X 7 function was threefold lower in canine monocytes compared to human monocytes.Thus, P2X 7 activation can induce the uptake of organic cations into canine erythrocytes and mononuclear leukocytes, but the relative levels of P2X 7 function differ to that of equivalent human cell types.

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The ATP4− receptor-operated ion channel of human lymphocytes: Inhibition of ion fluxes by amiloride analogs and by extracellular sodium ions

Cited by 80 publications

References 47 publications

The P_2Z‐purinoceptor of human lymphocytes: actions of nucleotide agonists and irreversible inhibition by oxidized ATP

The P_2Z‐purinoceptor of human lymphocytes: actions of nucleotide agonists and irreversible inhibition by oxidized ATP

CAY10593 inhibits the human P2X7 receptor independently of phospholipase D1 stimulation

The P2X7 receptor mediates the uptake of organic cations in canine erythrocytes and mononuclear leukocytes: comparison to equivalent human cell types

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The ATP4− receptor-operated ion channel of human lymphocytes: Inhibition of ion fluxes by amiloride analogs and by extracellular sodium ions

Cited by 80 publications

References 47 publications

The P2Z‐purinoceptor of human lymphocytes: actions of nucleotide agonists and irreversible inhibition by oxidized ATP

The P2Z‐purinoceptor of human lymphocytes: actions of nucleotide agonists and irreversible inhibition by oxidized ATP

CAY10593 inhibits the human P2X7 receptor independently of phospholipase D1 stimulation

The P2X7 receptor mediates the uptake of organic cations in canine erythrocytes and mononuclear leukocytes: comparison to equivalent human cell types

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The P_2Z‐purinoceptor of human lymphocytes: actions of nucleotide agonists and irreversible inhibition by oxidized ATP

The P_2Z‐purinoceptor of human lymphocytes: actions of nucleotide agonists and irreversible inhibition by oxidized ATP