title: The effect of ebselen on adenine nucleotide hydrolysis by platelets from adult rats.
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, respectively.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, ICBS, Rua Ramiro Barcelos, 2600-ANEXO, CEP 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Cristina Ribas
authors.initials: CR
authors.lastname: Fürstenau
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Spier
authors.forename: Bárbara
authors.initials: B
authors.lastname: Rücker
authors.forename: Simone
authors.initials: S
authors.lastname: Luisa Berti
authors.forename: Ana Maria Oliveira
authors.initials: AM
authors.lastname: Battastini
authors.forename: João José Freitas
authors.initials: JJ
authors.lastname: Sarkis
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D001393:Azoles / Q000633:toxicity*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006868:Hydrolysis; D020128:Inhibitory Concentration 50; D054833:Isoindoles; D008297:Male; D016566:Organoselenium Compounds / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate