Possible Interaction: Adenosine and Methotrexate

“CSF adenosine concentrations of patients receiving methotrexate , even when there was very slight or no toxicity, were greatly increased compared with control subjects (mean values of 217 and 51 nmol/L, median 175 and 52 nmol/L).”

“ MTX induced adenosine release from B cells and increased Bregs and precursors.”

“ MTX increases intracellular accumulation of adenosine monophosphate (AMP) and 5-aminoimidazole-4-carboxamide ribonucleotide which activates AMP-activated protein kinase (AMPK).”

“ Adenosine , acting at the A2A receptor, mediates the antiinflammatory effects of methotrexate (MTX) in models of inflammation.”

“1 Cronstein BN, Naime D, Ostad E. The antiinflammatory effects of methotrexate are mediated by adenosine.”

“Although methotrexate was first introduced as an antiproliferative agent that inhibits the synthesis of purines and pyrimidines for the therapy of malignancies, it is now clear that many of the anti-inflammatory effects of methotrexate are mediated by adenosine.”

“ Methotrexate and its polyglutamate derivatives suppress inflammatory responses through release of adenosine ; they suppress immune responses by inducing the apoptosis of activated T-lymphocytes and inhibiting the synthesis of both purines and pyrimidines.”

“Both MX-68 and MTX (at concentrations greater than 0.1 microM) increased the release of adenosine from Daudi cells in vitro.”

“Methotrexate MTX ) exerts an anti-inflammatory effect, reportedly by enhancing the release of adenosine , through an accumulation of 5-amino-4-imidazolecarboxamide ribonucleotide (AICAR).”

“Finally, as we have shown previously, adenosine mediates the antiinflammatory effects of methotrexate and sulfasalazine in the murine air pouch model of inflammation, and injection of APCP, the ecto-5'-nucleotidase inhibitor, abrogates completely the increase in adenosine and the decrement in inflammation in this in vivo model.”

“We and others have shown that an increased extracellular concentration of adenosine mediates the antiinflammatory effects of methotrexate and sulfasalazine both in vitro and in vivo, but the mechanism by which these drugs increase extracellular adenosine remains unclear.”

“These results indicate that sulfasalazine, like methotrexate , enhances adenosine release at an inflamed site and that adenosine diminishes inflammation via occupancy of A2 receptors on inflammatory cells.”

“We recently demonstrated that methotrexate promotes intracellular AICAR accumulation, thereby increasing adenosine release and diminishing inflammation, so we tested the hypothesis that sulfasalazine similarly promotes intracellular AICAR accumulation.”