Vodiskar_1999_Chem.Biol.Interact_119-120_333

Protein synthesis is impaired in the glucocorticoid (GC)-treated fast mammalian muscle. Electromechanical activity was reported to alleviate this effect. Acetylcholinesterase (AChE; EC 3.1.1.7) synthesis in the skeletal muscle is regulated by both, GCs and electromechanical activity. In light of the above reports, one would expect that electrical stimulation will prevent GC-mediated fall of AChE synthesis in the muscle. On the other hand, a substantial body of evidence suggests that electromechanical activity exerts its effect at the AChE mRNA level, while GCs most probably act at the translational or early posttranslational level. Different levels of action would be more consistent with the independent and therefore additive influences of the two regulatory factors. In order to ascertain whether glucocorticoid and electromechanical effects interact in the control of AChE activity, we compared the effects of GCs on normal, nonstimulated fast rat skeletal muscle, with those of GC-treated and simultaneously electrically stimulated (tonic pattern, 10 Hz) muscle. Untreated and stimulated-only muscles were used as respective controls. The effects on the fast extensor digitorum longus muscle and slow soleus muscle, treated similarly were compared. As expected, chronic GC treatment and electrical stimulation of fast rat muscles with slow activity patterns both downregulated AChE activity. However, no additional decrease in AChE activity was observed, if stimulated fast muscle was simultaneously treated with GCs, suggesting that slow pattern of electromechanical activity prevents GC-mediated downregulation of AChE. The most plausible explanation of this observation is, that muscle activity blocks expression of some generally acting factors, which are induced by GCs and are responsible for the impaired synthesis of several proteins including AChE.