Phosphodiesterase type 5 (PDE5) is co-localized with key proteins of the nitric oxide/cyclic GMP signaling in the human prostate

• Experimental studies have provided the basis for the evaluation of inhibitors of the phosphodiesterase type 5 (PDE5) in the treatment of lower urinary tract symptomatology (LUTS) secondary to benign prostatic hyperplasia (BPH). It has been speculated that the clinical efficacy of PDE5 inhibitors in patients with LUTS/BPH can be explained by their effects on the urinary bladder rather than on the prostate. Hence, the significance of the nitric oxide (NO)/cyclic GMP signaling in the control of the human prostate requires further clarification. less thanbrgreater than less thanbrgreater thanThe present study aimed to investigate by means of immunohistochemistry in the human prostate the expression and distribution of key mediators of the NO pathway, namely cyclic GMP, the neuronal nitric oxide synthase (nNOS), and cyclic GMP-binding protein kinases type I (cGKI alpha, cGKI), in relation to PDE5, protein kinase A (cAK), and the vasoactive intestinal polypeptide (VIP). less thanbrgreater than less thanbrgreater thanIn the smooth muscle portion of the transition zone, immunosignals specific for the PDE5 were found co-localized with cyclic GMP, cGKI alpha, and cGKI, as well as with the cyclic cAMP-binding protein kinase A. Smooth muscle bundles were seen innervated by slender varicose nerves characterized by the expression of nNOS. Some of these nerves also presented staining related to the neuropeptide VIP. less thanbrgreater than less thanbrgreater thanThe findings give hints that the cyclic GMP- and cyclic AMP-dependent signal transduction may synergistically work together in regulating muscle tension in the transition zone. This might be of significance for the identification of new pharmacological avenues to treat patients with symptomatic BPH.

Nyckelord

Human prostate

Lower urinary tract symptomatology (LUTS)

Phosphodiesterase type 5 (PDE5)

Cyclic GMP/cyclic AMP signaling

Immunohistochemistry

TECHNOLOGY

TEKNIKVETENSKAP

Publikations- och innehållstyp

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