Molecular Cloning and Expression of Human cGMP-Binding cGMP-Specific Phosphodiesterase (PDE5)

Stacey, Peter; Rulten, Stuart L.; Dapling, Alison; Phillips, Stephen C.

doi:10.1006/bbrc.1998.8769

Cited by 87 publications

(64 citation statements)

References 29 publications

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“…Functional studies on the PDE5 inhibitors and placebo influence on OA blood flow velocity are given in Table 1 PDE5 enzyme on human retinal tissue C Foresta et al 145 Eye and Figure 1. Measurements were done at each end point (baseline, 1,4,8,12,24,36, and 48 h) for the three drugs (sildenafil, tadalafil, and placebo). Colour Doppler measurements of the right and left eyes were compared using the Mann-Whitney U-test before and after drug intake.…”

Section: Resultsmentioning

confidence: 99%

Expression of the PDE5 enzyme on human retinal tissue: new aspects of PDE5 inhibitors ocular side effects

Foresta

Caretta

Zuccarello

et al. 2007

Eye

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Objective We tested the effect of two phosphodiesterase type-5 (PDE5) inhibitors, sildenafil and tadalafil, on ophthalmic artery (OA) blood flow velocity and investigated the presence of the PDE5 enzyme on human retinal tissue in comparison with the PDE6 enzyme localization. Methods Using Colour Doppler ultrasonography (CDU) we investigated, in 30 healthy young subjects (27.8 years of age; range, 24.3-33.7 years), the effects of a single oral dose of sildenafil (100 mg), tadalafil (20 mg), and placebo on OA blood flow velocity. Western blot for PDE6 and PDE5 protein expression was performed on frozen samples of human retina, testis, sperm, skin, and corpus cavernosum. Immunohistochemistry was performed on two ocular globes from dead donors. Results CDU showed a relationship between the administration of PDE5 inhibitors and OA blood flow velocity modifications in a timedependent manner. Western blot and immunohistochemical analysis showed PDE6 and PDE5 presence in human retinal tissue and gave a map of its distribution. Conclusion We demonstrated that (a) tadalafil and sildenafil are able to modify the OA flux in a time-dependent manner; (b) the PDE5 enzyme is expressed on retinal and choroid vasculature (smooth muscle and endothelial cells), on ganglion and bipolar cells; (c) human retinal tissues express the PDE6 enzyme in the rod and cone photoreceptors; (d) visual side effects after PDE5 inhibitors administration may be linked to a specific effect on the PDE5 enzyme; and (e) the PDE5 enzyme may have a physiologic role on ganglion and bipolar cells that need to be further investigated.

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Section: Resultsmentioning

confidence: 99%

Expression of the PDE5 enzyme on human retinal tissue: new aspects of PDE5 inhibitors ocular side effects

Foresta

Caretta

Zuccarello

et al. 2007

Eye

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“…17 Nitric oxide acts by increasing the activity of guanylyl cyclase, which increases the production of cyclic guanosine monophosphate (cGMP) and PDE5 inhibitors block the breakdown of cGMP. An effect of PDE5 inhibitors not only on erectile endothelium of the corpora cavernosa, but also on other organs was suggested by a mice model evaluating a new PDE5 inhibitor, DA-8159.…”

Section: Tadalafil and Epcs In Ed Patientsmentioning

confidence: 99%

Circulating endothelial progenitor cells and endothelial function after chronic Tadalafil treatment in subjects with erectile dysfunction

et al. 2006

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We evaluated the effect of a chronic treatment with Tadalafil on progenitor cells (PCs) number and endothelial function in patients with erectile dysfunction (ED) with or without cardiovascular risk factors. Twenty-six subjects with ED and 23 aged matched controls were studied. All subjects underwent blood tests, International Index of Erectile Function (IIEF-5), Nocturnal Penile Tumescence Rigidity Monitoring test (NPTRM), brachial artery flow-mediated dilation (FMD) and PCs count. International index of erectile function, FMD and PC count were re-evaluated in all subjects at the end of Tadalafil and placebo treatment. With respect to controls patients had lower basal FMD (Po0.05) and basal PCs (Po0.05). Treatment with Tadalafil determined a significant increase in PCs (Po0.001) and FMD (Po0.001) with respect to basal level. Positive correlation was found between basal FMD and PCs (Po0.05) and between basal FMD and PCs increase after Tadalafil treatment (Po0.05). Tadalafil promotes a mobilization of PCs and improves endothelial function in ED patients.

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“…Although several different types of phosphodiesterases have been identified within penile cavernosal tissue, human trabecular smooth muscle cells express phosphodiesterase type 5 (PDE 5) as the major cGMP hydrolyzing enzyme. 8,9 PDE 5 was initially identified as the major cGMP binding protein in bovine lung and later characterized as a cGMP-binding, cGMP-specific phosphodiesterase. [10][11][12] The purified protein is a homodimer of 99.6 kDa subunits and binds two zinc atoms per monomer which are necessary for catalysis.…”

Section: Introductionmentioning

confidence: 99%

Phosphodiesterase type 5 inhibitors: a biochemical and clinical correlation survey

Kim

2003

Int J Impot Res

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Phosphodiesterase type 5 (PDE 5) is the major cGMP hydrolyzing enzyme in penile corpus cavernosum and is an important regulator of nitric oxide-mediated smooth muscle relaxation. The critical role of PDE 5 in penile erection and the recent availability of specific and potent inhibitors of PDE 5 have enabled the development of effective oral treatment strategies that have been widely accepted by both health-care professionals and the lay public. This article examines the correlation between the available biochemical and clinical data for the PDE 5 inhibitors sildenafil (Viagra), tadalafil (Cialis) and vardenafil (Levitra).

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Molecular Cloning and Expression of Human cGMP-Binding cGMP-Specific Phosphodiesterase (PDE5)

Cited by 87 publications

References 29 publications

Expression of the PDE5 enzyme on human retinal tissue: new aspects of PDE5 inhibitors ocular side effects

Expression of the PDE5 enzyme on human retinal tissue: new aspects of PDE5 inhibitors ocular side effects

Circulating endothelial progenitor cells and endothelial function after chronic Tadalafil treatment in subjects with erectile dysfunction

Phosphodiesterase type 5 inhibitors: a biochemical and clinical correlation survey

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