Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5830497 | European Journal of Pharmacology | 2011 | 6 Pages |
Abstract
Adenosine 5â²-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 A2A receptor (CGS-21680) on ectonucleotidase activities and gene expression patterns in lymphocytes from mice submitted to an endotoxemia model. Animals were injected intraperitoneally with 12Â mg/kg Lipopolyssacharide (LPS) and/or 0.5Â 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 5â²-monophosphate (AMP), and p-Nitrophenyl thymidine 5â²-monophosphate (p-Nph-5â²-TMP) hydrolysis. However, when CGS-21680 was administered 24Â 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 A2A agonists.
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Authors
Fernanda Cenci Vuaden, Luiz Eduardo Baggio Savio, Carolina Maria Alves Bastos, MaurÃcio Reis Bogo, Carla Denise Bonan,