Deletion of CD73 increases exercise power in mice

Ecto-5′-nucleotidase or CD73 is the main source of extracellular adenosine involved in the activation of adenosine A(2A) receptors, responsible for the ergogenic effects of caffeine. We now investigated the role of CD73 in exercise by comparing female wild-type (WT) and CD73 knockout (KO) mice in a treadmill-graded test to evaluate running power, oxygen uptake (V̇O(2)), and respiratory exchange ratio (RER) — the gold standards characterizing physical performance. Spontaneous locomotion in the open field and submaximal running power and V̇O(2) in the treadmill were similar between CD73-KO and WT mice; V̇O(2)max also demonstrated equivalent aerobic power, but CD73-KO mice displayed a 43.7 ± 4.2% larger critical power (large effect size, P < 0.05) and 3.8 ± 0.4% increase of maximum RER (small effect size, P < 0.05). Thus, KO of CD73 was ergogenic; i.e., it increased physical performance.