MP17-20 PHOSPHODIESTERASE TYPE 5 (PDE5) IN THE HUMAN PROSTATE: RELATION TO KEY ENZYMES OF THE NITRIC OXIDE/CYCLIC GMP SIGNALING

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology1 Apr 2017MP17-20 PHOSPHODIESTERASE TYPE 5 (PDE5) IN THE HUMAN PROSTATE: RELATION TO KEY ENZYMES OF THE NITRIC OXIDE/CYCLIC GMP SIGNALING Stefan Ueckert, Andreas Bannowsky, Markus Kuczyk, and Petter Hedlund Stefan UeckertStefan Ueckert More articles by this author , Andreas BannowskyAndreas Bannowsky More articles by this author , Markus KuczykMarkus Kuczyk More articles by this author , and Petter HedlundPetter Hedlund More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.609AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES 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. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e218 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Stefan Ueckert More articles by this author Andreas Bannowsky More articles by this author Markus Kuczyk More articles by this author Petter Hedlund More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...