Immunohistochemical presence of cyclic AMP- and cyclic GMP- phosphodiesterase isoenzymes in human clitoris

Ückert, Stefan; Hedlund, Petter; Bogun, Yvonne; Stief, C.; Jonas, Udo; Andersson, K.E.; Oelke, Matthias

doi:10.1016/s1569-9056(03)80468-2

Cited by 7 publications

(4 citation statements)

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“…There is evidence from basic research that cyclic nucleotides and PDEs are involved in the maintenance of the normal function of the human vagina and clitoris, thus providing the physiological basis for an adequate genital response to sexual stimulation, subsequently leading to sexual arousal and orgasm. [13][14][15] The results from the present study demonstrate that various cyclic AMP-and cyclic GMP-PDE isoenzymes are expressed in human vaginal tissue and that these isoenzymes are not evenly distributed. Our findings indicate that PDE1, PDE2 and PDE5 are almost exclusively located in vascular smooth muscle of the vagina and cannot be detected in the epithelial layer.…”

Section: Discussionmentioning

confidence: 58%

Immunohistochemical distribution of cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the human vagina: A potential forensic value?

Albrecht

Ückert

Oelke

et al. 2007

Journal of Forensic and Legal Medicine

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Section: Discussionmentioning

confidence: 58%

Immunohistochemical distribution of cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the human vagina: A potential forensic value?

Albrecht

Ückert

Oelke

et al. 2007

Journal of Forensic and Legal Medicine

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“…Cyclic AMP‐PDE has been shown to be more abundant in clitoral stromal tissue and nerve fibers (Ueckert et al ., 2003). The adenylate cyclase‐dependent conversion of adenosine triphosphate (ATP) to cAMP is a pathway that is influenced by prostaglandin E 1 (PGE 1 ), the other main entity being evaluated in FSAD.…”

Section: Female Sexual Dysfunctionmentioning

confidence: 99%

“…Cyclic AMP-PDE has been shown to be more abundant in clitoral stromal tissue and nerve fibers (Ueckert et al, 2003). The adenylate cyclase-dependent conversion of adenosine S156…”

Section: Fsadmentioning

confidence: 99%

Late‐stage clinical development in lower urogenital targets: sexual dysfunction

Azam

2006

British J Pharmacology

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In recent years, late-stage clinical drug development that primarily focuses on urogenital targets has centered around four areas of medical need (both unmet need and aiming to improve on existing therapies). These include male sexual dysfunction (MSD), female sexual dysfunction (FSD), prostatic pathology (neoplastic, pre-neoplasitic, and non-neoplastic), and improvement in lower urinary tract symptoms. Despite the regulatory approval of compounds to treat erectile dysfunction (ED), benign prostatic hyperplasia, a number of treatments for overactive bladder, and stress urinary incontinence, there remains a deficiency in addressing a number of conditions that arise out of pathophysiological dysfunction resulting in lower urogenital tract sexual conditions. In terms of late-stage clinical development, significant progress has most recently been made in MSD development, especially in understanding further a common and complex sexual dysfunction -that of premature ejaculation. The search also continues for compounds that improve ED in terms of better efficacy and superior safety profile compared to the currently marketed phosphodiesterase-5-inhibitors. Whilst there are no approved medications to treat the subtypes of FSD, there has been significant progress in attempting to better understand how to appropriately assess treatment benefit in clinical trial settings for this difficult to diagnose and treat condition. This review will focus on late-stage human clinical development pertaining to MSD and FSD.

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“…Sildenafil and zaprinast competitively inhibited PDE activity in vitro, but sildenafil was approximately 50‐fold more potent than zaprinast [31]. More recently, immunohistochemical analysis of the fibromuscular stroma of the clitoris found PDE4 (mostly represented by PDE4A, which was most abundant in the stroma and nerve fibers) and PDE5 [32]. PDE5 immunoreactivity has also been found in human anterosuperior vaginal tissue, mostly localized in vascular smooth muscle but also in periurethral glands and vaginal epithelium [33].…”

Section: Female Sexual and Reproductive Functionmentioning

confidence: 99%

Review of Phosphodiesterases in the Urogenital System: New Directions for Therapeutic Intervention

Montorsi

Corbin

Phillips

2004

The Journal of Sexual Medicine

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Introduction With the success of Phosphodiesterase (PDE) type 5 inhibitors (i.e., sildenafil, tadalafil, vardenafil) in the treatment of erectile dysfunction (ED), PDEs are considered attractive targets for drug intervention in the urogenital tract. Aim To review the role of PDEs, which exist as a superfamily of enzymes comprising 11 distinct families, in the urogenital system, focusing on anatomical locations, functions and dysfunctions, potential disorders that could be treated, and any promising new selective PDE inhibitors under development. Methods Included are (i) abstracts from 2001, 2002, and 2003; (ii) a MEDLINE search from 1996 through December 2003; and (iii) a pipeline search for therapeutics in development. Data from animal experiments are presented when there is a paucity of human data, but with the caveat that the distribution of PDE isozymes in a specific tissue can vary between species. Results PDE mRNA and protein have been localized throughout the normal human urogenital tract. Double-blind, placebo-controlled studies suggest possible new clinical roles for sildenafil, including prophylaxis to preserve penile smooth muscle and erectile function after radical prostatectomy, and treatment of ejaculatory delay secondary to serotonergic reuptake inhibitor antidepressant therapy. Open-label studies suggest a potential clinical role for: vinpocetine (a PDE1 inhibitor) in the treatment of incontinence and low-compliance bladder; and sildenafil in the treatment of premature ejaculation, prostate-related lower urinary tract symptoms, and in women who have had unsuccessful in vitro fertilization. Several new orally administered PDE5 inhibitors are in early clinical development for the treatment of ED. Potential indications for PDE inhibitors that are suggested by preclinical data include Peyronie's disease, ureteral colic, male and female birth control, and prevention of preterm labor. Conclusion Drug selectivity and differential PDE tissue distribution allow for potential targeted intervention for numerous disorders related to the urogenital tract.

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Immunohistochemical presence of cyclic AMP- and cyclic GMP- phosphodiesterase isoenzymes in human clitoris

Cited by 7 publications

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Immunohistochemical distribution of cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the human vagina: A potential forensic value?

Immunohistochemical distribution of cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the human vagina: A potential forensic value?

Late‐stage clinical development in lower urogenital targets: sexual dysfunction

Review of Phosphodiesterases in the Urogenital System: New Directions for Therapeutic Intervention

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