Characteristics of photoreceptor PDE (PDE6): similarities and differences to PDE5

Int J Impot Res. 2004 Jun:16 Suppl 1:S28-33. doi: 10.1038/sj.ijir.3901212.


Phosphodiesterase 6 (PDE6) is highly concentrated in the retina. It is most abundant in the internal membranes of retinal photoreceptors, where it reduces cytoplasmic levels of cyclic guanosine monophosphate (cGMP) in rod and cone outer segments in response to light. The rod PDE6 holoenzyme comprises alpha and beta catalytic subunits and two identical inhibitory gamma subunits. Each catalytic subunit contains three distinct globular domains corresponding to the catalytic domain and two GAF domains (responsible for allosteric cGMP binding). The PDE6 catalytic subunits resemble PDE5 in amino-acid sequence as well as in three-dimensional structure of the catalytic dimer; preference for cGMP over cyclic adenosine monophosphate (cAMP) as a substrate; and the ability to bind cGMP at the regulatory GAF domains. Most PDE5 inhibitors inhibit PDE6 with similar potency, and electroretinogram studies show modest effects of PDE5 inhibitors on visual function-an observation potentially important in designing PDE5-specific therapeutic agents.

Publication types

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

MeSH terms

  • 3',5'-Cyclic-GMP Phosphodiesterases* / analysis
  • 3',5'-Cyclic-GMP Phosphodiesterases* / chemistry
  • 3',5'-Cyclic-GMP Phosphodiesterases* / metabolism
  • Animals
  • Binding Sites
  • Catalysis
  • Cyclic GMP / metabolism
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Cyclic Nucleotide Phosphodiesterases, Type 6
  • Dimerization
  • Humans
  • Phosphodiesterase Inhibitors / adverse effects
  • Phosphodiesterase Inhibitors / pharmacology
  • Phosphoric Diester Hydrolases* / analysis
  • Phosphoric Diester Hydrolases* / chemistry
  • Phosphoric Diester Hydrolases* / metabolism
  • Photoreceptor Cells / enzymology
  • Photoreceptor Cells, Vertebrate / drug effects
  • Photoreceptor Cells, Vertebrate / physiology*
  • Protein Processing, Post-Translational
  • Retina / drug effects
  • Retina / enzymology
  • Retina / physiology
  • Substrate Specificity
  • Vision, Ocular / drug effects


  • Phosphodiesterase Inhibitors
  • Phosphoric Diester Hydrolases
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Cyclic Nucleotide Phosphodiesterases, Type 6
  • PDE5A protein, human
  • PDE6B protein, human
  • Cyclic GMP