Expression and functional activity of phosphodiesterase type 5 in human and rabbit vas deferens

Mancina, Rosa; Filippi, Sandra; Marini, Mirca; Morelli, Annamaria; Vignozzi, Linda; Salonia, Andrea; Montorsi, Francesco; Mondaini, Nicola; Vannelli, Gabriella Barbara; Donati, Silvia; Lotti, Francesco; Forti, Gianni; Maggi, Mario

doi:10.1093/molehr/gah143

Cited by 71 publications

(70 citation statements)

References 37 publications

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“…The control group continued to receive a standard diet (control), whereas the treatment group was fed a HFD constituted by 0.5% cholesterol and 4% peanut oil (HFD rabbit) for 12 weeks, according to a slightly modified previously described protocol (Azadzoi & Saenz de Tejada 1991, Najibi et al 1994. A subset of control rabbits was treated for the last 8 weeks with the long-acting GNRH analogue triptorelin pamoate (Ipsen, Milan, Italy, 2.9 mg/kg), in order to induce a HH, according to a previously described protocol (Filippi et al 2002, Mancina et al 2005.…”

Section: Animalsmentioning

confidence: 99%

Spermatogenic and sperm quality differences in an experimental model of metabolic syndrome and hypogonadal hypogonadism

Mallidis¹,

Czerwiec²,

Filippi³

et al. 2011

Reproduction

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The synergistic effect of the co-morbidities that comprise metabolic syndrome (MetS) is increasingly being recognised as an important contributor in the pathology of a broad spectrum of seemingly disparate conditions. However, in terms of male reproductive function, beyond erectile dysfunction, little is known about the influence of this cohort (collectively or separately) on spermatogenesis and sperm quality. The aims of this study were to assess the reproductive tract of a MetS animal model for detrimental changes, to determine whether a group of compounds (advanced glycation end products and their receptor) known to cause cell dysfunction and DNA damage was present and assess whether hypogonadotropic hypogonadism was the main contributing factor for the changes seen. Animals fed a high-fat diet were found to have significantly increased cholesterol, triglycerides, blood glucose, mean arterial pressure and visceral fat levels. Although serum testosterone was decreased, no changes were seen in either testicular or epididymal histology. Immunolocalisation of N 3 -carboxymethyl-lysine and the receptor for advanced glycation end products was found in the testes, epididymides and sperm of the two treated groups of animals; however, ELISA did not show any difference in protein levels. Similarly, assessment of sperm nuclear DNA (nDNA) fragmentation by acridine orange test did not find significant differences in nDNA integrity. We conclude that the minimal effect on spermatogenesis and sperm quality seen in our model is probably due to the moderate increase of blood glucose rather than the hypogonadism.

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Section: Animalsmentioning

confidence: 99%

Spermatogenic and sperm quality differences in an experimental model of metabolic syndrome and hypogonadal hypogonadism

Mallidis¹,

Czerwiec²,

Filippi³

et al. 2011

Reproduction

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“…The role of the NO/cGMP pathway in PE has been investigated and it was found that NO-donors [107][108][109][110] are able to relax the vas deferens and seminal vesicles. 111 Moreover, it was also reported that eNOS knockout mice (lacking the gene for endothelial NO synthase) have higher rates of ejaculation, with less stimulation required to elicit ejaculation, compared to wild type mice. 112 Despite the involvement of the NO/cGMP system in PE, preclinical in vivo results with PDE inhibitors are still missing.…”

Section: Premature Ejaculationmentioning

confidence: 99%

PDE5 inhibitors beyond erectile dysfunction

et al. 2007

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The phosphodiesterase type-5 (PDE5) inhibitors sildenafil, vardenafil and tadalafil are widely used first-line therapy for erectile dysfunction (ED). Since the advent of sildenafil in 1998, more than 40 million men worldwide have been successfully treated with these compounds. The safety and high tolerability of PDE5 inhibitors make them an attractive tool to investigate further physiological functions of PDE5, for example the modulation of intracellular cyclic GMP (cGMP) pools. As cGMP is a key component of intracellular signaling this may provide novel therapeutic opportunities beyond ED even for indications in which chronic administration is necessary. The approval of sildenafil for the treatment of pulmonary hypertension in 2005 was a notable success in this area of research. A number of other potential new indications are currently in various phases of preclinical research and development. In recent years, extensive but very heterogeneous information has been published in this field. The aim of this review is to summarize existing preclinical and clinical knowledge and critically discuss the evidence to support potential future indications for PDE5 inhibitors.

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“…52 Some experiments have shown a relationship between ejaculation function and PDE-5. Mancina et al 53 demonstrated the expression of PDE-5 in all human and rabbit vas deferens muscles. Kriegsfeld et al 54 showed that ejaculation can be inhibited by nitric oxide in nongenetically altered mice, and this effect most likely is modulated by reduced sympathetic nervous system activity.…”

Section: Pde-5ismentioning

confidence: 99%

Current therapeutic strategies for premature ejaculation and future perspectives

Xin¹,

Zhu²,

Yuan³

et al. 2011

Asian J Androl

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Premature ejaculation (PE) is a common sexual disorder in men that is mediated by disturbances in the peripheral and central nervous systems. Although all pharmaceutical treatments for PE are currently used 'off-label', some novel oral agents and some newer methods of drug administration now provide important relief to PE patients. However, the aetiology of this condition has still not been unified, primarily because of the lack of a standard animal model for basic research and the absence of a widely accepted definition and assessment tool for evidence-based clinical studies in patients with PE. In this review, we focus on the current therapeutic strategies and future treatment perspectives for PE. Ejaculation is a tightly coordinated activity with different ejaculatory organs and a spinal reflex initiated by genital and/or brain stimulation through the peripheral sensory receptors and regions, afferent pathways, the central nervous system ejaculatory centre of the brain (namely, sensory and motor areas located in the para-ventricular nucleus of the hypothalamus and the medial preoptic area). The spinal ejaculatory centre, located at the T 12 -L 1-2 spinal cord level (paragigantocellular), and its efferent pathway modulate the function of the ejaculatory organs. Ejaculation is also mediated by a complex interaction of central serotonergic and dopaminergic neurons with the secondary involvement of cholinergic, adrenergic, oxytocinergic and GABAergic neurons.Ejaculation consists of two main phases, the emission phase and the expulsion phase. The emissions include seminal fluid and secretions of the prostate and bulbourethral glands. In this phase, the contraction of accessory ejaculatory organs induces the accumulation of semen in the posterior urethra. Expansion of the posterior urethra creates a feeling of emission and sensory information that is transmitted to the spine via dorsal nerve sensory pathway and along the spinal cord up to the brain ejaculatory centre during the sexual arousal phase. The expulsion phase consists of the highly regular rhythmic contraction of striated muscles and the relaxation of smooth muscles in the ejaculatory ducts. The ejaculated semen can be divided into a number of components by serial biochemical analysis. 1 These include secretions from the seminal vesicles, prostate and bulbourethral (Cowper's) glands and spermatozoa.

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Expression and functional activity of phosphodiesterase type 5 in human and rabbit vas deferens

Cited by 71 publications

References 37 publications

Spermatogenic and sperm quality differences in an experimental model of metabolic syndrome and hypogonadal hypogonadism

Spermatogenic and sperm quality differences in an experimental model of metabolic syndrome and hypogonadal hypogonadism

PDE5 inhibitors beyond erectile dysfunction

Current therapeutic strategies for premature ejaculation and future perspectives

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