The effect of ebselen on adenine nucleotide hydrolysis by platelets from adult rats

Chemico-biological Interactions
Cristina Ribas FürstenauJ J F Sarkis

Abstract

The extracellular hydrolysis of adenine nucleotides by intact rat blood platelets occurs by the action of a cascade of enzymes constituted by an NTPDase 3 (CD39, EC 3.6.1.5, apyrase) and a 5'-nucleotidase (CD73, EC 3.5.7.3), whose final product is adenosine. Ebselen is a seleno-organic compound that possesses low toxicity and exhibits antioxidant, anti-inflammatory, anti-atherosclerotic, and cytoprotective properties. The main objective of this study was to evaluate if the anti-inflammatory drug ebselen can modulate the extracellular adenine nucleotide hydrolysis by platelets from rats. Our results showed that ebselen, at final concentrations of 30 and 100 microM, inhibits in vitro ATP extracellular hydrolysis by 48 and 60%, respectively. Ebselen, at final concentrations of 100 and 130 microM, also inhibited the in vitro extracellular hydrolysis of ADP by 28 and 35%, respectively. However, this drug did not alter AMP hydrolysis by platelets in the appropriate assay conditions. Kinetic analysis showed that the inhibition of ADP and ATP hydrolysis by ebselen, in rat platelets, is of the uncompetitive type. The IC50 calculated from the results were 99 +/- 10 and 186 +/- 47 microM (mean +/- S.D., n = 3) for ATP and ADP hydrolysis, ...Continue Reading

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Citations

Jul 2, 2011·Archives of Toxicology·Cristina W Nogueira, João B T Rocha
Jul 18, 2006·Cell Biology and Toxicology·J Saluk-JuszczakR Glowacki
May 15, 2009·The Journal of Biological Chemistry·Lucia Seminario-VidalEduardo R Lazarowski
Jun 7, 2006·The Journal of Biological Chemistry·Seiko F OkadaRichard C Boucher
Mar 26, 2011·Purinergic Signalling·Lucia Semianrio-VidalEduardo Rodolfo Lazarowski
Aug 12, 2015·Purinergic Signalling·Geoffrey Burnstock
Jul 19, 2006·Cellular & Molecular Biology Letters·Paweł NowakBarbara Wachowicz
Mar 18, 2005·Journal of Applied Physiology·Antonino CoppolaGiacomo Lucivero
Nov 4, 2008·Platelets·Anna Rita TognaGiuseppina I Togna
Feb 24, 2009·Platelets·Fernanda Cenci VuadenCarla Denise Bonan
Apr 22, 2015·Molecular and Cellular Biochemistry·Nicéia Spanholi CalgarotoMaria Rosa Chitolina Schetinger

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