The role of beta-adrenoceptor signaling in skeletal muscle: therapeutic implications for muscle wasting disorders.
OBJECTIVE
The beta-adrenergic signaling pathway represents a novel therapeutic target for skeletal muscle wasting disorders due to its roles in regulating protein synthesis and degradation. beta-Adrenoceptor agonists (beta-agonists) have therapeutic potential for attenuating muscle wasting associated with sarcopenia (age-related muscle wasting), cancer cachexia, sepsis, disuse, burns, HIV-AIDS, chronic kidney or heart failure, and neuromuscular diseases such as the muscular dystrophies. This review describes the role of beta-adrenergic signaling in the mechanisms controlling muscle wasting due to its effects on protein synthesis, protein degradation, and muscle fiber phenotype.


RESULTS
Stimulation of the beta-adrenergic signaling pathway with beta-agonists has therapeutic potential for muscle wasting since administration can elicit an anabolic response in skeletal muscle. As a consequence of their potent muscle anabolic actions, the effects of beta-agonist administration have been examined in several animal models and human conditions of muscle wasting in the hope of discovering a new therapeutic. The repartitioning characteristics of beta-agonists (increasing muscle mass and decreasing fat mass) have also made them attractive anabolic agents for use in livestock and by some athletes. However, potentially deleterious cardiovascular side-effects of beta-agonists have been identified and these will need to be obviated in order for the therapeutic potential of beta-agonists to be realized.


CONCLUSIONS
Multiple studies have identified anticachectic effects of beta-agonists and their therapeutic potential for pathologic states when muscle protein hypercatabolism is indicated. Future studies examining beta-agonist administration for muscle wasting conditions need to separate beneficial effects on skeletal muscle from potentially deleterious effects on the heart and cardiovascular system.
Koopman
René
R
Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Victoria, Australia.
Ryall
James G
JG
Church
Jarrod E
JE
Lynch
Gordon S
GS
D018663:Adrenergic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D002100:Cachexia / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction; D019282:Wasting Syndrome / Q000188:drug therapy / Q000378:metabolism*
D018663:Adrenergic Agents; D011506:Proteins; D011943:Receptors, Adrenergic, beta