Mol. Hum. Reprod. Advance Access published online on January 7, 2005
Molecular Human Reproduction, doi:10.1093/molehr/gah143
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1 Andrology Unit, Department of Clinical Physiopathology, Florence, 50139, Italy
* To whom correspondence should be addressed. The molecular mechanisms underlying the regulation of vas deferens (VD) motility and semen emission are still poorly understood. We now report evidence on VD expression of phosphodiesterase type 5 (PDE5), which regulates nitric oxide (NO)-induced relaxation and cGMP breakdown in smooth muscle cells. In human VD, the PDE5 abundance was relatively high (>3 x 106 molecules/µg total RNA), although 10-fold lower than in corpora cavernosa (CC). Also cGMP metabolising activity was higher in CC than in VD. However, both tissues share the same sensitivity to a broad panel of cGMP-related PDE inhibitors: sildenafil, tadalafil, dipyridamole, zaprinast, vinpocetine, EHNA and cilostamide. Based on the rank order of potency of these PDE inhibitors, we found that the cGMP metabolizing activity in human VD mostly corresponds to PDE5. PDE5 was immunolocalized in all the muscular layers of human and rabbit VD and was found to be negatively involved in regulating NO-induced relaxation. In addition, by using a rabbit model of hypogonadotropic hypogonadism, we found that PDE5 gene expression and activity are androgen-dependent in VD, as previously demonstrated in CC. In fact, the sensitivity to a NO-donor (NCX4040), its enhancement by PDE5 inhibitors and the PDE5-related cGMP breakdown were all affected by androgen manipulation. Our results provide a hypothesis explaining the beneficial effects of PDE inhibitors in patients with rapid ejaculation. *The authors equally contributed to this work.
Received November 9, 2004
Accepted December 16, 2004
Article
Expression and functional activity of phosphodiesterase type 5 in human and rabbit vas deferens
2 Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Pharmacology and Clinical Physiopathology, Florence, 50139, Italy
3 Department of Anatomy, Histology and Forensic Medicine, Florence, 50139, Italy
4 Department of Urology, University Vita-Salute San Raffaele, Scientific Institute H. San Raffaele, 20132 Milan, Italy
5 Department of Urology, University of Florence, 50139, Florence , Italy
M. Maggi, E-mail: m.maggi{at}dfc.unifi.it
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