Login to Access Video or Poster Abstract: MP17-20
Sources of Funding: none

Introduction

The significance of the nitric oxide (NO)/cyclic GMP pathway in the control of prostate smooth musculature actually serves as a rationale for the clinical development of the phosphodiesterase type 5 (PDE5, cyclic GMP PDE) inhibitor tadalafil to treat lower urinary tract symptomatology (LUTS) secondary to benign prostatic hyperplasia (BPH). However, the potential relevance of the nitric oxide (NO)/cyclic GMP signaling in the human prostate is still discussed controversly. For example, it has been speculated that the clinical efficacy of PDE5 inhibitors in patients with LUTS/BPH can be explained by the effects of this class of drugs on the urinary bladder rather than the prostate (Chapple C.R., Roehrborn C.G., Eur. Urol. 49: 651-659, 2006). This prompted us to evaluate in the human prostate the expression of key proteins of the NO pathway, namely the neuronal nitric oxide synthase (nNOS), cyclic GMP, and cyclic GMP-binding protein kinase type I (isoforms alpha und beta = cGKIα, cGKIβ), in relation to the PDE5.

Methods

Slices (10 µm) of specimens taken from the transition zone (TZ) of the human prostate were exposed to antibodies directed against cyclic GMP, PDE5A, nNOS, cGKIα or cGKIβ, followed by the application of fluorochrome-labeled secondary antibodies. Visualization was commenced by means of laser fluorescence microscopy.

Results

In the smooth muscle (SM) portion of the TZ, immunosignals specific for the PDE5 were found co-localized with cyclic GMP, cGKIα and cGKIβ, as well as with the cyclic cAMP-binding protein kinase A (cAK). SM bundles were seen innervated by slender varicose nerve fibers characterized by the expression of nNOS. Some of these nerves also presented staining related to the neuropeptide VIP (vasoactive intestinal polypeptide).

Conclusions

The results are in support of the hypothesis of a role of the cyclic GMP signaling in the control of the TZ of the prostate and also give hints that the cyclic GMP- and cyclic AMP-dependent signal transduction may synergistically work together.

Funding

none