G protein-coupled receptor kinases 2 and 5 are differentially expressed in rat skeletal muscle and remain unchanged following beta2-agonist administration.

Chronic stimulation of beta2-receptors with beta2-agonists causes desensitisation, which in skeletal muscle is accompanied by myosin heavy chain (MHC) remodelling, similar to that observed in heart failure patients. However, the mechanisms for this skeletal muscle remodelling are not well established. G protein-coupled receptor kinases (GRKs) specifically phosphorylate and desensitise G protein-coupled receptors during periods of agonist activation. However, desensitisation associated with prolonged agonist activation alters beta-adrenergic signalling, and downstream affects gene expression. We hypothesised that skeletal muscle remodelling induced by beta2-agonist administration could be regulated by GRK expression. Therefore the aim of this study was firstly to characterise which, if any, of the six known isoforms of GRK were expressed in skeletal muscle and then secondly to determine whether remodelled skeletal muscle induced by chronic beta2-agonist administration was accompanied by altered expression of GRK isoforms. Male Wistar rats were administered a beta2-agonist daily for 8 weeks, and the expression of MHC and GRKs examined in gastrocnemius and soleus muscles. Treatment with beta2-agonist caused a change in MHC in soleus from types I to IIA, and in gastrocnemius from MHC types IIA/IIX to IIB. Western blotting revealed that GRK2 and GRK5 were expressed in skeletal muscle. Furthermore, despite changes in MHC and differential muscle-specific expression of GRK isoforms, there was no significant change in expression of GRK2 and GRK5 in soleus or gastrocnemius following beta2-agonist administration. In conclusion the level of GRK expression is unlikely to be responsible for MHC switching following chronic beta2-receptor stimulation.