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Title: Adenosine A(2A) receptor agonist (CGS-21680) prevents endotoxin-induced effects on nucleotidase activities in mouse lymphocytes
Authors: Vuaden, Fernanda Cenci
Savio, Luiz Eduardo Baggio
Bastos, Carolina Maria Alves [UNIFESP]
Bogo, Mauricio Reis
Bonan, Carla Denise
Pontificia Univ Catolica Rio Grande do Sul
Univ Fed Rio Grande do Sul
Universidade Federal de São Paulo (UNIFESP)
Keywords: Lipopolysaccharide
Nucleoside triphosphate diphosphohydrolase
Nucleotide pyrophosphatase/phosphodiesterase
5 '-Nucleotidase
Issue Date: 25-Jan-2011
Publisher: Elsevier B.V.
Citation: European Journal of Pharmacology. Amsterdam: Elsevier B.V., v. 651, n. 1-3, p. 212-217, 2011.
Abstract: Adenosine 5'-triphosphate (ATP) released during inflammation presents proinflammatory properties. Adenosine, produced by catabolism of ATP, is an anti-inflammatory compound. Considering the role of ATP and adenosine in inflammation and the importance of ectonucleotidases in the maintenance of their extracellular levels, we investigated the effect of a selective agonist of the adenosine A(2A) receptor (CGS-21680) on ectonucleotidase activities and gene expression patterns in lymphocytes from mice submitted to an endotoxemia model. Animals were injected intraperitoneally with 12 mg/kg Lipopolyssacharide (LPS) and/or 0.5 mg/kg CGS-21680 or saline. Nucleotidase activities were determined in lymphocytes from mesenteric lymph nodes and analysis of ectonucleotidase expression was carried out by a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Exposure to endotoxemia promoted an increase in nucleotide hydrolysis. When CGS-21680 was administered concomitantly with LPS, this increase was prevented for ATP, adenosine 5'-monophosphate (AMP), and p-Nitrophenyl thymidine 5'-monophosphate (p-Nph-5'-TMP) hydrolysis. However, when CGS-21680 was administered 24 h after LPS injection, the increase was not reversed. the expression pattern of ectonucleotidases was not altered between LPS and LPS plus CGS-21680 groups, indicating that the transcriptional control was not involved on the effect exerted for CGS-21680. These results showed an enhancement of extracellular nucleotide catabolism in lymphocytes after induction of endotoxemia, which was prevented, but not reversed by CGS-21680 administration. These findings suggest that the control of nucleotide and nucleoside levels exerted by CGS-21680 could contribute to the modulation of the inflammatory process promoted by adenosine A(2A) agonists. (C) 2010 Elsevier B.V. All rights reserved.
ISSN: 0014-2999
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