Phosphodiesterase 4 inhibition reduces skeletal muscle atrophy.
Several GTP-binding protein (G-protein)-coupled receptors that signal through Galphas (GTP-binding protein alpha 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.
Hinkle
Richard T
RT
Research Division, Procter & Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason-Montgomery Road, Mason, Ohio 45040, USA.
Dolan
Elizabeth
E
Cody
David B
DB
Bauer
Mary Beth
MB
Isfort
Robert J
RJ
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D002976:Clenbuterol / Q000627:therapeutic use; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009121:Muscle Denervation / Q000379:methods; D018482:Muscle, Skeletal / Q000187:drug effects*; D009133:Muscular Atrophy / Q000188:drug therapy* / Q000209:etiology; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D051381:Rats; D020426:Sciatic Neuropathy / Q000150:complications / Q000188:drug therapy
D000318:Adrenergic beta-Agonists; D010726:Phosphodiesterase Inhibitors; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D002976:Clenbuterol