Cyclic nucleotide phosphodiesterase isozymes expressed in mouse skeletal muscle

Can J Physiol Pharmacol. 2002 Dec;80(12):1132-5. doi: 10.1139/y02-149.

Abstract

To understand changes in cyclic nucleotide metabolism in muscle disease states, the expression of phosphodiesterase (PDE) isozymes in normal mouse leg muscle was examined. Four subcellular fractions were generated by differential centrifugation at 10,000 x g and 100,000 x g. cAMP PDE activity was found predominately in the soluble fractions, while cGMP PDE activity was more evenly distributed amongst soluble and particulate fractions. Pharmacological inhibitors demonstrate that PDE4 represents the major cAMP hydrolyzing activity and PDE2 represents the major cGMP hydrolyzing activity in mouse leg muscle. PDE1 is expressed at low levels, while PDE3 and PDE5 are intermediate. Between 20 and 40% of total PDE activity remained in the presence of inhibitors for PDE1-PDE5, indicating that other PDE families contribute to the total PDE pool. Reverse-transcription PCR with family-specific primers showed expression of mRNA for PDE7-PDE9, supporting this conclusion. Total PDE activity was found to be elevated in tissue extracts from a mouse model of Duchenne's muscular dystrophy.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors
  • 3',5'-Cyclic-AMP Phosphodiesterases / biosynthesis
  • 3',5'-Cyclic-AMP Phosphodiesterases / genetics
  • Animals
  • Cyclic Nucleotide Phosphodiesterases, Type 1
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Enzymologic / physiology
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / biosynthesis
  • Isoenzymes / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred mdx
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / enzymology*
  • Muscular Dystrophy, Duchenne / enzymology
  • Phosphodiesterase Inhibitors / pharmacology
  • Phosphoric Diester Hydrolases / biosynthesis*
  • Phosphoric Diester Hydrolases / genetics

Substances

  • Isoenzymes
  • Phosphodiesterase Inhibitors
  • Phosphoric Diester Hydrolases
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 1