Regulation of murine cardiac function by phosphodiesterases type 3 and 4

Curr Opin Pharmacol. 2011 Dec;11(6):714-9. doi: 10.1016/j.coph.2011.10.017. Epub 2011 Oct 31.

Abstract

Cyclic nucleotide phosphodiesterases (PDEs) encompass a large group of enzymes that regulate intracellular levels of two-second messengers, cAMP and cGMP, by controlling the rates of their degradation. More than 60 isoforms, subdivided into 11 gene families (PDE1-11), exist in mammals with at least six families (PDE1-5 and PDE8) identified in mammalian hearts. The two predominant families implicated in regulating contraction strength of the heart are PDE3 and PDE4. Studies using transgenic models in combination with family-specific PDE inhibitors have demonstrated that PDE3A, PDE4B, and PDE4D isoforms regulate cardiac contractility by modulating cAMP levels in various subcellular compartments. These studies have further uncovered contributions of PDE4B and PDE4D in preventing ventricular arrhythmias.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cyclic AMP / physiology
  • Cyclic Nucleotide Phosphodiesterases, Type 3 / chemistry
  • Cyclic Nucleotide Phosphodiesterases, Type 3 / genetics
  • Cyclic Nucleotide Phosphodiesterases, Type 3 / metabolism*
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / chemistry
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / genetics
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism*
  • Excitation Contraction Coupling / drug effects
  • Heart / drug effects
  • Heart / physiology*
  • Heart / physiopathology
  • Heart Diseases / drug therapy
  • Heart Diseases / metabolism
  • Heart Diseases / physiopathology
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Mice
  • Mice, Knockout
  • Molecular Targeted Therapy
  • Myocardial Contraction / drug effects
  • Myocardium / enzymology*
  • Myocardium / metabolism
  • Phosphodiesterase Inhibitors / chemistry
  • Phosphodiesterase Inhibitors / pharmacology
  • Phosphodiesterase Inhibitors / therapeutic use
  • Second Messenger Systems / drug effects

Substances

  • Isoenzymes
  • Phosphodiesterase Inhibitors
  • Cyclic AMP
  • Cyclic Nucleotide Phosphodiesterases, Type 3
  • Cyclic Nucleotide Phosphodiesterases, Type 4