1. Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2016.175
Figure 4 Proposed mechanism by which methotrexate increases adenosine signalling
Figure 4 | Proposed mechanism by which methotrexate increases adenosine signalling. Methotrexate (in particular polyglutamated methotrexate) antagonizes the activity of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase (ATIC), resulting in accumulation of AICAR, which antagonizes the activity of adenosine deaminase (ADA) and AMP deaminase (AMPDA), increasing concentrations of AMP and adenosine, which are externalized by the cell. AMP in the extracellular environment is cleaved to adenosine by the ecto-5′-nucleotidase CD73, which is potentiated by AICAR. Extracellular adenosine signals in an autocrine and paracrine fashion via adenosine receptors (ADOR). FAICAR, 5-formamidoimidazole-4-carboxamide ribotide.
Brown, P. M. et al. (2016) Mechanism of action of methotrexate in rheumatoid arthritis, and the search for biomarkers
Nat. Rev. Rheumatol. doi: /nrrheum