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  • Original Research
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Characteristics of Photoreceptor PDE (PDE6): similarities and differences to PDE5

Abstract

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 α and β catalytic subunits and two identical inhibitory γ 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.

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Acknowledgements

Research from the author's laboratory described in this paper was funded by the National Institutes of Health (EY-05798). This is Scientific Contribution Number 2162 from the New Hampshire Agricultural Experiment Station.

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Correspondence to R H Cote.

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Cote, R. Characteristics of Photoreceptor PDE (PDE6): similarities and differences to PDE5. Int J Impot Res 16 (Suppl 1), S28–S33 (2004). https://doi.org/10.1038/sj.ijir.3901212

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