Purpose: Although it has been supposed that the NO/cyclic GMP system produces inhibitory signals to reduce the resistance of the bladder outlet and urethra during the micturition phase, little is known on the mechanisms controlling the function of urethral smooth muscle. The aim of the present study was to examine in the male and female urethra the expression of phosphodiesterase (PDE) isoenzymes, known as key proteins of the cyclic GMP/AMP signaling. Methods: Urethral tissue was obtained from 4 female cadavers and 7 male patients (who had undergone gender reassignment surgery). The expression of mRNA encoding for PDE1A, 1B, 1C, 2A, 4B, 4D, 5A, 10A and 11A was investigated by means of real-time polymerase chain reaction. Western blot (WB) analysis was conducted to detect PDE isoenzymes. Results: RT-PCR revealed relevant amounts of mRNA encoding for PDE1A, 2A, 4B, 5A, 10A and 11A in male and female urethral tissue. The expression of PDE1A, 2A, 4B and 10A was 2-fold higher in the female than in the male urethra, whereas the expression of PDE11A mRNA was 7-fold higher in the male tissue. In the WB experiments, immunosignals specific for PDE1A, PDE4A and 4B and PDE11A were of higher degree in the female than the male tissue specimens, while an almost equivocal expression of PDE2A, PDE5A and PDE10A was registered. Conclusion: On the level of mRNA and function proteins, different patterns of expression of PDE isoenzymes were registered in human male and female urethra. Future studies may clarify whether inhibition of PDE isoenzymes is likely to facilitate the relaxation of the outflow region in both sexes.
- Cyclic adenosine monophosphate
- Nitric oxide/cyclic guanosine monophosphate
- Phosphodiesterase isoenzymes
- Urethral smooth muscle