Adrenodemedullation activates the Ca-dependent proteolysis in soleus muscles from rats exposed to cold.

Previous studies have shown that catecholamines in vivo and in vitro inhibit the activity of Ca-dependent proteolysis in skeletal muscles under basal conditions. In the present study we sought to investigate the role of catecholamines in regulating the Ca-dependent proteolysis in soleus and extensor digitorum longus (EDL) muscles from rats acutely exposed to cold. Overall proteolysis, the activity of proteolytic systems, protein levels and gene expression of different components of the calpain system were investigated in rats submitted to adrenodemedullation (ADMX) and exposed to cold for 24 h. ADMX drastically reduced plasma epinephrine and promoted an additional increase in the overall proteolysis, which was already increased by cold exposure. The rise in the rate of protein degradation in soleus muscles from adrenodemedullated cold-exposed rats was caused by the high activity of the Ca-dependent proteolysis, which was associated with the generation of a 145-kDa cleaved α-fodrin fragment, a typical calpain substrate, and lower protein levels and mRNA expression of calpastatin, the endogenous calpain inhibitor. Unlike that observed for soleus muscles, the cold-induced muscle proteolysis in EDL was not affected by ADMX. In isolated soleus muscle, clenbuterol, a selective β-adrenoceptor agonist, reduced the basal Ca-dependent proteolysis and completely abolished the activation of this pathway by the cholinergic agonist carbachol. These data suggest that catecholamines released from the adrenal medulla inhibit cold-induced protein breakdown in soleus, and this antiproteolytic effect on the Ca-dependent proteolytic system is apparently mediated through expression of calpastatin, which leads to suppression of calpain activation. Although many effects of the sympathetic nervous system on muscle physiology are known, the role of catecholamines in skeletal muscle protein metabolism has been scarcely studied. We suggest that catecholamines released from adrenal medulla may be of particular importance for restraining the activation of the Ca-dependent proteolysis in soleus muscles during acute cold exposure. This finding helps us to understand the adaptive changes that occur in skeletal muscle protein metabolism during cold stress.