Phosphodiesterase 5 in the female pig and human urethra: morphological and functional aspects

Werkström, Viktoría; Svensson, Anna; Andersson, Karl Erik; Hedlund, Petter

doi:10.1111/j.1464-410x.2006.06217.x

Cited by 67 publications

(69 citation statements)

References 45 publications

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“…In contrast, little is known about the PDE enzymes in LUT vascular smooth muscle. Werkstrom et al 44 demonstrated a similar distribution of PDE 5 in the vasculature of the female pig (Fig. 5) and human urethra.…”

Section: Pdes In Lut Vasculaturementioning

confidence: 79%

“…However, in the presence of L-NOARG, there was a significant decrease in cGMP content in comparison to the control tissue. Werkstrom et al 44 also characterized the distribution of PDE 5, cGMP, and PKG1 in female pig and human urethra tissue, and evaluated the effect of pharmacologic inhibition of PDE 5 in isolated smooth muscle preparations. After stimulation with the NO-donor diethylenetriamine NONOate, the cGMP-immunoreactivity (IR) in urethral and vascular smooth muscles increased.…”

Section: Pdes In the Urethramentioning

confidence: 97%

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Phosphodiesterases (PDEs) and PDE inhibitors for treatment of LUTS

et al. 2007

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Lower urinary tract (LUT) smooth muscle can be relaxed by drugs that increase intracellular concentrations of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Both of these substances are degraded by phosphodiesterases (PDEs), which play a central role in the regulation of smooth muscle tone. The distribution and functional significance of PDE enzymes vary in different tissues of the LUT. Targeting specific PDE isoenzymes should thus allow organ selectivity. PDE 4 and 5 appear to predominate in the prostate, PDE 1 and 4 are thought to influence detrusor smooth muscle function, and PDE 5 may be functionally important in the urethra and vasculature. Studies on the use of PDE inhibitors to treat various LUT symptoms (LUTS), have yielded favorable results. Thus, positive effects of the PDE 5 inhibitors sildenafil and tadalafil on symptoms and quality of life in men with LUTS, erectile dysfunction, and BPH have also been demonstrated. These effects may be due to effects on cGMP signaling and/or modification of afferent input from bladder, urethral, and prostate tissue. This review gives an update on the distribution of PDEs in structures relevant for LUT function, and discusses how inhibition of these enzymes can contribute to beneficial effects on LUTS. Information for the review was obtained from searches of the PubMed database, and from the authors' files.

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Section: Pdes In Lut Vasculaturementioning

confidence: 79%

Section: Pdes In the Urethramentioning

confidence: 97%

Phosphodiesterases (PDEs) and PDE inhibitors for treatment of LUTS

et al. 2007

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“…The presence of phosphodiesterase type 5 (PDE-5) and cGMP has been shown in the female urethra. Inhibition of PDE-5 with drugs like sildenafil, vardenafil and tadalafil caused NO/ cGMP-mediated relaxation [88] . Recently, c-kit (CD117)-positive interstitial cells have been demonstrated in the urinary tract (i.e.…”

Section: Nitric Oxide (No)mentioning

confidence: 99%

Pharmacologic Targets on the Female Urethra

Canda

Çınar²,

Turna

et al. 2008

Urol Int

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Introduction: This article reviews the mechanisms affecting contraction and relaxation of the urethra in order to establish a basis for current and future treatments for urinary incontinence in women. Material and Methods: A review of the English literature using MEDLINE was performed between 1970 and 2008 on female urethra pharmacology, urinary incontinence, and mechanisms involved in contraction and relaxation of the female human urethra. Results: α-Adrenoceptors (ARs) cause contraction and β-ARs cause relaxation. Use of selective α-agonist and β-AR blocker agents might have potential for the treatment of stress urinary incontinence. Tolerable doses of cholinergic agonists did not have significant effects on intraurethral pressure. Nitric oxide seems to be the major nonadrenergic-noncholinergic inhibitory transmitter causing relaxation. c-kit-positive interstitial cells seem to regulate urethral tone. The roles of adenosine triphosphate and carbon monoxide have not been fully investigated in humans. Neuropeptides function similarly to the urinary bladder. Prostanoids cause urethral contraction and relaxation depending on their subtypes. Serotonin enhances the strength of urethral sphincteric contractions. The Rho-kinase pathway also appears to be modulating smooth muscle contraction in the urethra. Conclusions: Understanding of the urethral function and pharmacology may lead to the development of promising new agents which might be useful in the management of urinary incontinence in women.

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“…NO is an important inhibitory neurotransmitter in smooth muscle of the urethra and increase the level of cGMP that exerts a relaxant effect. [14,15] Cyclic adenosine monophosphate is more important than cGMP for detrusor function, hence the cAMP pathway in the bladder has been more thoroughly investigated than cGMP. Five isoforms of PDEs (1)(2)(3)(4)(5) were isolated and demonstrated in human and porcine detrusor in functional studies.…”

Section: Discussionmentioning

confidence: 99%

Effect of sildenafil citrate in testosterone induced benign prostate hyperplasia rat model

Çalışkan

Keleş

Öztürk

et al. 2017

Turkish Journal of Urology

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Objective: Efficacy of treatments for benign prostate hyperplasia (BPH) is limited because the disease has complex etiopathogenesis. Recent studies have demonstrated the presence of phosphodiesterase-5 (PDE-5) receptors in prostate tissue. We investigated efficacy of sildenafil citrate in testosteron -induced BPH in rats. Material and methods:The rats were divided into three groups. Each groups had 7 rats. Group 1 was control group. Testosteron propionate 3 mg/kg/day was injected subcutaneously for two weeks in Group 2. The same procedure was done for Group 3 and sildenafil citrate was added to water at daily doses of 2 mg/kg for two weeks. The rats were euthanized with intraperitoneal pentobarbital. The body weights were measured and the prostates were removed. Results:The mean weights of rats were 288±31.93, 345±23.23 and 294±32.86 g in Groups 1, 2 and 3, respectively. The mean prostate weights of rats were 0.74±0.18, 1.3±0.13 and 0.72±0.24 g in Groups 1, 2, and 3, respectively. Group 2 had statistically significantly higher prostate weights than the other groups (p<0.01). Relative prostate weight is calculated with ratio of prostate weight to body weight. BPH group showed an increase in relative prostate weight compared with other groups with significant difference (p= 0.036 and p= 0.040). There was statistical difference for acinar area between Group 2 and the others, no significant difference of number of acini, interstitial space and epithelial thickness. Group 2 has more papillary projections per acini than the other groups. Conclusion:Favourable effect of sildenafil citrate on dimensions of prostate but not all on histological parameters was observed. We expect that PDE-5 inhibitors might be a treatment option for BPH patients if the studies support our findings in the future.

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Phosphodiesterase 5 in the female pig and human urethra: morphological and functional aspects

Cited by 67 publications

References 45 publications

Phosphodiesterases (PDEs) and PDE inhibitors for treatment of LUTS

Phosphodiesterases (PDEs) and PDE inhibitors for treatment of LUTS

Pharmacologic Targets on the Female Urethra

Effect of sildenafil citrate in testosterone induced benign prostate hyperplasia rat model

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