Adenosine A_2A receptor agonist (CGS-21680) prevents endotoxin-induced effects on nucleotidase activities in mouse lymphocytes

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• 作者：Fernanda Cenci Vuaden^a ; Luiz Eduardo Baggio Savio^a ; ^b ; Carolina Maria Alves Bastos^c ; Maurí ; cio Reis Bogo^b ; Carla Denise Bonan^b ; ^{cbonan@pucrs.br}
• 关键词：Lipopolysaccharide ; Lymphocytes ; Nucleoside triphosphate diphosphohydrolase ; Nucleotide pyrophosphatase/phosphodiesterase ; 5′ ; -Nucleotidase ; Adenosine
• 刊名：European Journal of Pharmacology
• 出版年：2011
• 出版时间：25 January 2011
• 年：2011
• 卷：651
• 期：1-3
• 页码：212-217
• 全文大小：277 K

文摘

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.