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. Author manuscript; available in PMC: 2020 May 1.
Published in final edited form as: Joint Bone Spine. 2018 Aug 3;86(3):301–307. doi: 10.1016/j.jbspin.2018.07.004

Figure 1. Methotrexate’s effect on adenosine formation.

Figure 1.

Methotrexate blocks AICAR leading to accumulation of AICAR, which blocks adenosine deaminase. Adenosine formed intracellularly is transported out of the cell by ENT1. ATP and ADP in the extracellular space are dephosphorylated sequentially by transmembrane CD39 to form AMP and AMP is converted to adenosine by transmembrane CD73 and adenosine can be converted to inosine or act via the adenosine receptors to activate various downstream pathways. Adapted from Cronstein and Sitkovsky (2017) (14). Abbreviations: AICAR, amidoimidazolecarboxamidoribonucleotide; ENT1, extracellular nucleoside transporter; ATP, adenosine triphosphate; ADP, adenosine diphosphate; CD39, nucleoside triphosphate phophohydrolase; AMP, adenosine monophosphate; CD73, ecto-5’nucleotidase (CD73).