Is the cyclic AMP specific phosphodiesterase type 4 (PDE4) a NEW pharmacological target in the human prostate? an in vitro approach
Abstract
Abstract Objectives The utmost significance of the nitric oxide (NO)/cyclic GMP pathway in the control of prostate smooth musculature serves as the rationale for the clinical application of the phosphodiesterase type 5 (PDE5, cyclic GMP PDE) inhibitor tadalafil to treat lower urinary tract symptomatology (LUTS) (secondary to benign prostatic hyperplasia). However, aside from the PDE5, other PDE isoenzymes that have been demonstrated in the human prostate have yet received little scientific attention. The present study aimed to evaluate in more detail in the human prostate by means of immunohistochemical and functional experiments the potential pharmacological relevance of the cyclic AMP-specific PDE4. Methods The expression and distribution of PDE4 protein in the human prostate was investigated by means of immunohistochemistry using anti-PDE4A, -4B, -4C and -4D and also anti-nNOS (neuronal nitric oxide synthase) and -VIP (vasoactive intestinal polypeptide) antibodies. The effects of the PDE4 inhibitors rolipram, Ro 20-1724 and RP 73401 (piclamilast) on the tension brought about by the alpha-adrenergic agonist norepinephrine (NE, 10 μM) of isolated prostate tissue was investigated using the tissue bath technique. Forskolin (an adenylyl cyclase activator) was used as a reference compound. Results In the transition zone, immunosignals specific for PDE4B and PDE4C were mainly seen in glandular structures while PDE4D was registered in glandular clusters and also, to a certain…
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