Adenosine A(2A) receptor agonist (CGS-21680) prevents endotoxin-induced effects on nucleotidase activities in mouse lymphocytes

Adenosine A(2A) receptor agonist (CGS-21680) prevents endotoxin-induced effects on nucleotidase activities in mouse lymphocytes

Autor Vuaden, Fernanda Cenci Google Scholar
Savio, Luiz Eduardo Baggio Google Scholar
Bastos, Carolina Maria Alves Autor UNIFESP Google Scholar
Bogo, Mauricio Reis Google Scholar
Bonan, Carla Denise Google Scholar
Instituição Pontificia Univ Catolica Rio Grande do Sul
Univ Fed Rio Grande do Sul
Universidade Federal de São Paulo (UNIFESP)
Resumo 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.
Assunto Lipopolysaccharide
Lymphocytes
Nucleoside triphosphate diphosphohydrolase
Nucleotide pyrophosphatase/phosphodiesterase
5 '-Nucleotidase
Adenosine
Idioma Inglês
Financiador Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS)
Data 2011-01-25
Publicado em European Journal of Pharmacology. Amsterdam: Elsevier B.V., v. 651, n. 1-3, p. 212-217, 2011.
ISSN 0014-2999 (Sherpa/Romeo, fator de impacto)
Editor Elsevier B.V.
Extensão 212-217
Fonte http://dx.doi.org/10.1016/j.ejphar.2010.11.003
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000286849400028
URI http://repositorio.unifesp.br/handle/11600/33359

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