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. 1994 Jul;112(3):946–950. doi: 10.1111/j.1476-5381.1994.tb13172.x

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

J S Wiley 1, J R Chen 1, M B Snook 1, G P Jamieson 1
PMCID: PMC1910210  PMID: 7921625

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%.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Balke C. W., Wier W. G. Modulation of L-type calcium channels by sodium ions. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4417–4421. doi: 10.1073/pnas.89.10.4417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benham C. D., Tsien R. W. A novel receptor-operated Ca2+-permeable channel activated by ATP in smooth muscle. Nature. 1987 Jul 16;328(6127):275–278. doi: 10.1038/328275a0. [DOI] [PubMed] [Google Scholar]
  3. Burnstock G. Overview. Purinergic mechanisms. Ann N Y Acad Sci. 1990;603:1–18. doi: 10.1111/j.1749-6632.1990.tb37657.x. [DOI] [PubMed] [Google Scholar]
  4. Dubyak G. R., De Young M. B. Intracellular Ca2+ mobilization activated by extracellular ATP in Ehrlich ascites tumor cells. J Biol Chem. 1985 Sep 5;260(19):10653–10661. [PubMed] [Google Scholar]
  5. Dubyak G. R., el-Moatassim C. Signal transduction via P2-purinergic receptors for extracellular ATP and other nucleotides. Am J Physiol. 1993 Sep;265(3 Pt 1):C577–C606. doi: 10.1152/ajpcell.1993.265.3.C577. [DOI] [PubMed] [Google Scholar]
  6. Figures W. R., Niewiarowski S., Morinelli T. A., Colman R. F., Colman R. W. Affinity labeling of a human platelet membrane protein with 5'-p-fluorosulfonylbenzoyl adenosine. Concomitant inhibition of ADP-induced platelet aggregation and fibrinogen receptor exposure. J Biol Chem. 1981 Aug 10;256(15):7789–7795. [PubMed] [Google Scholar]
  7. Filippini A., Taffs R. E., Agui T., Sitkovsky M. V. Ecto-ATPase activity in cytolytic T-lymphocytes. Protection from the cytolytic effects of extracellular ATP. J Biol Chem. 1990 Jan 5;265(1):334–340. [PubMed] [Google Scholar]
  8. Gordon J. L. Extracellular ATP: effects, sources and fate. Biochem J. 1986 Jan 15;233(2):309–319. doi: 10.1042/bj2330309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Greenberg S., Di Virgilio F., Steinberg T. H., Silverstein S. C. Extracellular nucleotides mediate Ca2+ fluxes in J774 macrophages by two distinct mechanisms. J Biol Chem. 1988 Jul 25;263(21):10337–10343. [PubMed] [Google Scholar]
  10. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  11. Guardabasso V., Munson P. J., Rodbard D. A versatile method for simultaneous analysis of families of curves. FASEB J. 1988 Mar 1;2(3):209–215. doi: 10.1096/fasebj.2.3.3350235. [DOI] [PubMed] [Google Scholar]
  12. Murgia M., Hanau S., Pizzo P., Rippa M., Di Virgilio F. Oxidized ATP. An irreversible inhibitor of the macrophage purinergic P2Z receptor. J Biol Chem. 1993 Apr 15;268(11):8199–8203. [PubMed] [Google Scholar]
  13. Pizzo P., Zanovello P., Bronte V., Di Virgilio F. Extracellular ATP causes lysis of mouse thymocytes and activates a plasma membrane ion channel. Biochem J. 1991 Feb 15;274(Pt 1):139–144. doi: 10.1042/bj2740139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sariban-Sohraby S., Benos D. J. The amiloride-sensitive sodium channel. Am J Physiol. 1986 Feb;250(2 Pt 1):C175–C190. doi: 10.1152/ajpcell.1986.250.2.C175. [DOI] [PubMed] [Google Scholar]
  15. Schilling W. P., Rajan L., Strobl-Jager E. Characterization of the bradykinin-stimulated calcium influx pathway of cultured vascular endothelial cells. Saturability, selectivity, and kinetics. J Biol Chem. 1989 Aug 5;264(22):12838–12848. [PubMed] [Google Scholar]
  16. Soltoff S. P., McMillian M. K., Talamo B. R. ATP activates a cation-permeable pathway in rat parotid acinar cells. Am J Physiol. 1992 Apr;262(4 Pt 1):C934–C940. doi: 10.1152/ajpcell.1992.262.4.C934. [DOI] [PubMed] [Google Scholar]
  17. Tatham P. E., Cusack N. J., Gomperts B. D. Characterisation of the ATP4- receptor that mediates permeabilisation of rat mast cells. Eur J Pharmacol. 1988 Feb 16;147(1):13–21. doi: 10.1016/0014-2999(88)90628-0. [DOI] [PubMed] [Google Scholar]
  18. Tatham P. E., Lindau M. ATP-induced pore formation in the plasma membrane of rat peritoneal mast cells. J Gen Physiol. 1990 Mar;95(3):459–476. doi: 10.1085/jgp.95.3.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wiley J. S., Chen R., Jamieson G. P. The ATP4- receptor-operated channel (P2Z class) of human lymphocytes allows Ba2+ and ethidium+ uptake: inhibition of fluxes by suramin. Arch Biochem Biophys. 1993 Aug 15;305(1):54–60. doi: 10.1006/abbi.1993.1392. [DOI] [PubMed] [Google Scholar]
  20. Wiley J. S., Chen R., Wiley M. J., Jamieson G. P. The ATP4- receptor-operated ion channel of human lymphocytes: inhibition of ion fluxes by amiloride analogs and by extracellular sodium ions. Arch Biochem Biophys. 1992 Feb 1;292(2):411–418. doi: 10.1016/0003-9861(92)90010-t. [DOI] [PubMed] [Google Scholar]
  21. Wiley J. S., Dubyak G. R. Extracellular adenosine triphosphate increases cation permeability of chronic lymphocytic leukemic lymphocytes. Blood. 1989 Apr;73(5):1316–1323. [PubMed] [Google Scholar]
  22. Wiley J. S., Jamieson G. P., Mayger W., Cragoe E. J., Jr, Jopson M. Extracellular ATP stimulates an amiloride-sensitive sodium influx in human lymphocytes. Arch Biochem Biophys. 1990 Aug 1;280(2):263–268. doi: 10.1016/0003-9861(90)90328-v. [DOI] [PubMed] [Google Scholar]
  23. Yamaguchi D. T., Green J., Kleeman C. R., Muallem S. Properties of the depolarization-activated calcium and barium entry in osteoblast-like cells. J Biol Chem. 1989 Jan 5;264(1):197–204. [PubMed] [Google Scholar]
  24. el-Moatassim C., Dubyak G. R. A novel pathway for the activation of phospholipase D by P2z purinergic receptors in BAC1.2F5 macrophages. J Biol Chem. 1992 Nov 25;267(33):23664–23673. [PubMed] [Google Scholar]
  25. el-Moatassim C., Mani J. C., Dornand J. Extracellular ATP4- permeabilizes thymocytes not only to cations but also to low-molecular-weight solutes. Eur J Pharmacol. 1990 May 31;181(1-2):111–118. doi: 10.1016/0014-2999(90)90251-z. [DOI] [PubMed] [Google Scholar]

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