The Role of P2Y Receptors in the Regulation of Atrophic Processes in Rat Skeletal Muscles under Unloading

Skeletal muscle atrophy during their unloading is due to a decrease in protein synthesis and an increase in proteolysis. The accumulation of ATP in muscle during unloading, detected at its early stages, may be one of the stimuli triggering this process. It has been shown that pannexin channels allow ATP efflux from the cytoplasm to the extracellular space during muscle unloading. Extracellular ATP can be sensed by P2Y2 receptors. To test the hypothesis on the involvement of P2Y2 receptors in the regulation of signaling processes in skeletal muscles at early stages of unloading, they were inhibited by their selective inhibitor AR-C 18925XX. The inhibition of P2Y2 receptors during 3-day unloading attenuated m. soleus atrophy, prevented ATP accumulation therein, downregulated the expression of MAFbx E3-ligase mRNA, ubiquitin and IL6 receptors, upregulated the level of AMPK phosphorylation and intensity of protein synthesis.