This research proposal will characterize biochemical and pharmacologic parameters of adrenergic and serotonergic regulation of protein and amino acid metabolism in skeletal muscle. Interrelationships, if any, will be ascertained between Beta-adrenergic receptor stimulation of muscle adenylate cyclase and D-serotonergic receptor mediated stimulation of muscle adenylate cyclase. The possibility of indirect serotonergic action owing to release of endogenous catecholamines in skeletal muscle will also be examined. Studies will be performed on adrenergic and serotonergic stimulation of cyclic AMP accumulation and on two parameters of autacoid action in skeletal muscle: muscle amino acid release and phosphorylase b to a conversion. Mechanisms producing adrenergic and serotonergic desensitization in such pathologic states as chronic renal failure and muscular dystrophy will be investigated. Using highly sensitive 125I and 3H-labeled probes of adrenergic receptor function, receptor number and affininty will be characterized. Coupling of adrenergic and serotonergic receptors to adenylate cyclase and guanylyl nucleotide regulation of adenylate cyclase will be investigated in these pathologic states. These studies will define mechanisms by which adrenergic and serotonergic agonists influence muscle protein and amino acid metabolism and will elucidate mechanisms of desensitization which may underlie the muscle wasting and dysfunction of chronic renal failure and murine muscular dystrophy.