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Title: The P2Z-purinoceptor of human lymphocytes: actions of nucleotide agonists and irreversible inhibition by oxidized ATP.
Austin Authors: Wiley, J S;Chen, J R;Snook, M B;Jamieson, Gary P
Affiliation: Haematology Department, Austin Hospital, Heidelberg, Victoria, Australia
Issue Date: 1-Jul-1994
Publication information: British Journal of Pharmacology; 112(3): 946-50
Abstract: 1. 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. 2. 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-gamma-S. ADP, UTP and alpha,beta-methylene ATP were unable to stimulate Ba2+ influx. 3. Extracellular Na+ inhibited the increment of Ba2+ influx induced by all concentrations of ATP, 2-methylthio ATP, 2-chloroATP and ATP-gamma-S. This inhibitory effect of extracellular Na+ is also reflected in the different EC50s for benzoylbenzoic ATP (8 microM in K(+)-media, 18 microM in Na(+)-media) but the maximal response to this agonist was the same in the presence or absence of Na+. 4. Treatment of lymphocytes with 2,3 dialdehyde ATP (oxidized ATP0 at 300 microM 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%. 5. 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.
Gov't Doc #: 7921625
Type: Journal Article
Subjects: Adenosine Triphosphate.pharmacology
Culture Media
Cytosol.drug effects.metabolism
In Vitro Techniques
Leukemia, Lymphocytic, Chronic, B-Cell.metabolism
Lymphocytes.drug effects.metabolism
Purine Nucleotides.pharmacology
Purinergic P2 Receptor Agonists
Purinergic P2 Receptor Antagonists
Tumor Cells, Cultured
Appears in Collections:Journal articles

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