The overall goal of this project is to explore the use of beta2- receptor agonists to retard the loss of skeletal muscle mass and function resulting from disuse and denervation in vivo. These studies are an outgrowth of our work on the control of muscle growth by calcium, cAMP and passive tension since the beta-receptor may act by altering calcium and cAMP pools. Recently, we found that clenbuterol, a selective beta2 receptor agonist, can markedly retard atrophy of the rat soleus and other slow muscles resulting from denervation. We will examine, in detail, the ability of clenbuterol to retard disuse atrophy produced by suspension of the rat hind limb s well as denervation and compare such effects to those produced by clenbuterol in growing and non-growing muscles. Slow and fast muscles will be examined with respect to fiber type area, twitch and tetanus tension, fatigability and myosin isoforms. In addition, changes in protein synthesis, proteolysis, releasible myofilaments and cAMP will be measured in atrophying muscles after in vivo treatment with beta agonists to give some insight on the responsible cellular mechanisms involved. Optimization of beta2- agonist treatment of suspension and denervation atrophy may lead to a useful therapeutic modality for treatment of muscle atrophy resulting from prolonged bed rest, immobilization and certain neuromuscular diseases.