ED 22. Cyclic 3, 5 guanosine monophosphate and cyclic 3, 5 adenosine monophosphate modulate the contractility of smooth muscle from seminal vesicle

Objective: As the most common second massagers, cyclic guanosine 3, 5 monophosphate (cGMP) and cyclic adenosine 3, 5 monophosphate (cAMP) have widely confirmed to modulate the contractility of smooth muscle in many tissues. However, the documentation as to the contractility of SV is relatively sparse. We examined the effects of vardenafil and caffeine on nervemediated contraction and phenylephrine-induced contractures to testify whether cGMP and cAMP are involved in modulating the contractility of smooth muscles from seminal vesicle (SV).

Methods: Muscle strips were prepared from guinea-pig SV and contractions were elicited by 3 s trains of electrical field stimuli (0.1 ms, 10-100 Hz) or 0.1 M phenylephrine respectively. Various concentrations of vardenafil (1, 3, 10 and 30 μM) and caffeine (0.1, 0.3, 1, 3 and 10 mM) in a cumulative manner were used to identify and characterize cGMP and cAMP.

Results: Both vardenafil and caffeine produced differential inhibition on contractions at most stimulation frequencies, and the inhibitive effect of vardenafil or caffeine significantly increased with the improving of concentration. The half-maximal inhibition concentration of vardenafil and caffeine at 40 Hz were 2.6±1.4 μM and 2.6±0.5 mM respectively. Additionally, caffeine significantly inhibited the nerve-mediated contraction, and when combined with vardenafil, the inhibitive effect of caffeine was significantly enhanced. Moreover, there was no significant difference of inhibitive rate between vardenafil and vardenafil on the basis of the inhibitive effect of caffeine. Neither vardenafil nor caffeine had effect on the phenylephrine-induced contracture of smooth muscle from SV, and there was no significant change with the increasing of the concentration.

Conclusions: The cGMP-specific phosphodiesterase and cAMP-specific phosphodiesterase are present in intramuscular nerve not smooth muscle itself, and cGMP and cAMP serve as two main second massagers separately to modulate the contractility of smooth muscle from SV. Abnormality in cGMP and cAMP may lead to dysfunction of SV and hence contribute to the mechanisms of premature ejaculation.