Adenosine signalling mediates the anti-inflammatory effects of the COX-2 inhibitor nimesulide.

Adenosine signalling mediates the anti-inflammatory effects of the COX-2 inhibitor nimesulide. Biochem Pharmacol. 2016 May 14; Authors: Caiazzo E, Maione F, Morello S, Lapucci A, Paccosi S, Steckel B, Lavecchia A, Parenti A, Iuvone T, Schrader J, Ialenti A, Cicala C Abstract Extracellular adenosine formation from ATP is controlled by ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase/CD39) and ecto-5'-nucleotidase (e-5NT/CD73); the latter converts AMP to adenosine and inorganic phosphate, representing the rate limiting step controlling the ratio between extracellular ATP and adenosine. Evidence that cellular expression and activity of CD39 and CD73 may be subject to changes under pathophysiological conditions has identified this pathway as an endogenous modulator in several diseases and was shown to be involved in the molecular mechanism of drugs, such as methotrexate, salycilates, interferon -β. We evaluated whether CD73/adenosine/A2A signalling pathway is involved in nimesulide anti-inflammatory effect, in vivo and in vitro. We found that the adenosine A2A agonist, 4-[2-[[6-Amino-9-(N-ethyl-β-D-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzenepropanoic acid hydrochloride (CGS21680, 2mg/kg ip.), inhibited carrageenan - induced rat paw oedema and the effect was reversed by co-administration of the A2Aantagonist -(2-[7-amino-2-[2-furyl][1,2,4]triazolo[2,3-a][1,3,5]triazin-5-yl-amino]ethyl)phenol (ZM241385; 3 mg/kg i.p...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research