International Journal of Urology (2005) 12, 829–834 Blackwell Science, LtdOxford, UKIJUInternational Journal of Urology0919-81722005 Blackwell Publishing Asia Pty LtdJuly 2005129829834Original Article Sildenafil and vas deferensSS Bilge et al. Correspondence: S. Sırrı Bilge MD, University of Ondokuz Mayıs, Department of Pharmacology, Kurupelit, 55139, Samsun, Turkey. Email: ssbilge@omu.edu.tr Received 25 August 2004; accepted 17 February 2005. Original Article Possible role of sildenafil in inhibiting rat vas deferens contractions by influencing the purinergic system S SIRRI BILGE, YUKSEL KESIM, MEHMET KURT, ELIF AKSOZ AND SULEYMAN CELIK University of Ondokuz Mayis, Department of Pharmacology, Kurupelit, Samsun, Turkey Abstract Aim: To evaluate the effect of sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-selective type 5 phosphodiesterase, on isolated rat vas deferens and its connections with the purinergic system. Methods: Epididymal and prostatic portions of isolated vas deferens were placed in organ baths containing Krebs’ solution. Contractions were induced by noradrenaline (NA), adenosine triphos- phate (ATP), α,β-methylene ATP and electrical field stimulation (EFS). The effect of sildenafil on the contractions was compared with suramin and Evans blue (EB). Results: NA, ATP, α,β-methylene ATP and EFS caused contractions in both portions of vas deferens. NA-induced contractions were unaffected by sildenafil and suramin but potentiated by EB. ATP- induced contractions were non-competitively inhibited in both portions by sildenafil and suramin but potentiated by EB. α,β-methylene ATP-induced contractions were unaffected by sildenafil but were inhibited in both portions by suramin and EB. EFS-induced contractions were inhibited by sildenafil and suramin while potentiated by EB. Conclusion: Sildenafil inhibited the contractions in both portions of vas deferens, as did suramin. We have suggested that purinergic system has a role in this antagonism and it seems to be mediated by an ATP-dependent mechanism instead of a receptor interaction. Key words ejaculation, purinergic system, rat, sildenafil, vas deferens. Introduction Ejaculatory disturbances are common clinical problems, reported in approximately 40% of adult males and fre- quently present together with erectile dysfunction. 1 Ejaculation occurs, in fact, in response to rhythmic con- tractions of male secondary sex organs including the vas deferens. Besides the physiological control of the con- traction, it is widely accepted that noradrenaline (NA) and adenosine triphosphate (ATP) are costored and coreleased by the adrenergic nerve endings in the vas deferens. 2 ATP causes a rapid, transient contraction by acting over P 2x receptors, while NA causes a slower and more sustained contraction via α 1 -adrenoceptors. The neurotransmission in the epididymal portion is mainly noradrenergic, while it is purinergic in the prostatic portion. 3 Several drugs may influence the function of the vas deferens and ultimately male infertility. Sildenafil is a specific inhibitor of phospho- diesterase enzyme type 5 (PDE5) and represents a power- ful therapy for male erectile dysfunction. 4 It shows a potent relaxant effect on corpus cavernosum smooth muscles by prolonging cyclic guanosine mono- phosphate (cGMP) actions. After sexual stimulation, neurogenically-mediated release of nitric oxide induces the formation of cGMP by guanylate cyclase within the corpus cavernosum smooth muscle. Premature ejacula- tion may be defined as inadequate ejaculatory control and is a problem that affects the sexual satisfaction of both partners. Premature ejaculation is the most com- mon type of male sexual dysfunction, with an estimated incidence of 30%. 5 Recent anatomical and physiological findings suggest a role for the nitric oxide/cGMP (NO/