Phosphodiesterase 4 inhibition reduces skeletal muscle atrophy

• Published in: Muscle & nerve Vol. 32; no. 6; pp. 775 - 781
• Main Authors: Hinkle, Richard T., Dolan, Elizabeth, Cody, David B., Bauer, Mary Beth, Isfort, Robert J.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.12.2005
• Subjects: 3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors; Adrenergic beta-Agonists - therapeutic use; Analysis of Variance; Animals; Ariflo; clenbuterol; Clenbuterol - therapeutic use; Cyclic Nucleotide Phosphodiesterases, Type 4; Disease Models, Animal; disuse atrophy; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Electric Stimulation - methods; Mice; muscle atrophy; Muscle Contraction - drug effects; Muscle Denervation - methods; Muscle, Skeletal - drug effects; Muscular Atrophy - drug therapy; Muscular Atrophy - etiology; pentoxifylline; phosphodiesterase 4; Phosphodiesterase Inhibitors - therapeutic use; Rats; rolipram; Sciatic Neuropathy - complications; Sciatic Neuropathy - drug therapy; skeletal muscle
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/mus.20416

Several GTP‐binding protein (G‐protein)–coupled receptors that signal through Gαs (GTP‐binding protein α stimulatory) and the cyclic adenosine monophosphate (cAMP) pathway increase skeletal muscle mass. In order to further evaluate the role of the cAMP pathway in the regulation of skeletal muscle mass, we utilized inhibitors of phosphodiesterase 4 (PDE 4), the major cAMP‐modifying PDE found in skeletal muscle, to modulate skeletal muscle cAMP levels. We found that PDE 4 inhibitors reduced the loss of muscle mass and force resulting from denervation and casting in rats and mice. These studies indicate that PDE 4 inhibitors may have a role in the treatment of skeletal muscle–wasting diseases. Muscle Nerve, 2005