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895 Cyclic GMP-binding protein kinases are colocalised with isoforms of the cyclic AMP-specific phosphodiesterase type 4 (PDE4) in the human prostate: An immunohistochemical study
895
Cyclic GMP-binding protein kinases are colocalised with isoforms of the cyclic AMP-specific phosphodiesterase type 4 (PDE4) in the human prostate: An immunohistochemical study Eur Urol Suppl 2014;13;e895
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Ückert S. 1 , Waldkirch E.S.1 , Montorsi F.2 , Kuczyk M.A.1 , Hedlund P. 2 1 Hanover
Medical School, Dept. of Surgery, Dept. of Urology & Urological Oncology, Hanover, Germany, 2 University Vita Salute San
Raffaele, Dept. of Urology, Urological Research Institute, Milan, Italy INTRODUCTION & OBJECTIVES: There is vast evidence that the nitric oxide (NO) pathway and related key enzymes, e.g., the cyclic GMP phosphodiesterase 5 (PDE5, cGMP PDE) and cyclic GMP-binding protein kinases (cGK), play a role in the control of the normal function of the human prostate. Moreover, the cyclic AMP signalling has been assumed an alternative pharmacological target to treat dysfunctions of the human lower urinary tract. While the clinical significance of the cyclic NO/cyclic GMP system in the prostate has been addressed comprehensively, until today, only a very few studies have focused on the cyclic AMP signalling. The present study aimed to investigate by means of immunohistochemistry in the human prostate the distribution of cyclic GMP-binding protein kinases (cGK) in relation to the cyclic AMP PDE4. MATERIAL & METHODS: Macroscopically normal tissue from the transition zone (TZ) was obtained from 8 male patients (mean age 65 years) who had undergone surgery for malignancies of the prostate or urinary bladder. The expression and distribution of the cGKI (isoforms alpha und beta = cGKIα, cGKIß) and the cyclic AMP PDE4 (isoforms PDE4A, 4B, 4C and 4D) were evaluated using specific antibodies in tissue sections (8 - 10 µm) by means of single and double-labelling techniques. RESULTS: In the smooth muscle (SM) portion of the TZ, abundant immunosignals specific for cGKIα and cGKIß were seen. These signals were colocalised with the cyclic nucleotide cyclic GMP and also the PDE5. In the cGK-positive SM and glandular tissue, the presence of the PDE 4A and 4C was observed. PDE4 was also seen colocalised with the cyclic AMP-binding protein kinase (cAK). In addition, PDE4A was detected in varicose nerve fibres transversing the tissue sections, some of these nerves presented staining related to the neuropeptide vasoactive intestinal polypeptide (VIP). Signals related to PDE4B and 4D were more prominent in the stromal smooth musculature than in the glandular epithelial multilayer. CONCLUSIONS: The results are in support of the hypothesis that, in the human prostate, the cyclic GMP- and cyclic AMP-dependent signal transduction systems may synergistically work together. Targeting the cyclic AMP signalling might represent a new option to treat lower urinary tract symptomatology (LUTS) secondary to benign prostatic hyperplasia (BPH).
Cyclic GMP-binding protein kinases are colocalised with isoforms of the cyclic AMP-specific phosphodiesterase type 4 (PDE4) in the human prostate: An immunohistochemical study Eur Urol Suppl 2014;13;e895
Print! Print!
Ückert S. 1 , Waldkirch E.S.1 , Montorsi F.2 , Kuczyk M.A.1 , Hedlund P. 2 1 Hanover
Medical School, Dept. of Surgery, Dept. of Urology & Urological Oncology, Hanover, Germany, 2 University Vita Salute San
Raffaele, Dept. of Urology, Urological Research Institute, Milan, Italy INTRODUCTION & OBJECTIVES: There is vast evidence that the nitric oxide (NO) pathway and related key enzymes, e.g., the cyclic GMP phosphodiesterase 5 (PDE5, cGMP PDE) and cyclic GMP-binding protein kinases (cGK), play a role in the control of the normal function of the human prostate. Moreover, the cyclic AMP signalling has been assumed an alternative pharmacological target to treat dysfunctions of the human lower urinary tract. While the clinical significance of the cyclic NO/cyclic GMP system in the prostate has been addressed comprehensively, until today, only a very few studies have focused on the cyclic AMP signalling. The present study aimed to investigate by means of immunohistochemistry in the human prostate the distribution of cyclic GMP-binding protein kinases (cGK) in relation to the cyclic AMP PDE4. MATERIAL & METHODS: Macroscopically normal tissue from the transition zone (TZ) was obtained from 8 male patients (mean age 65 years) who had undergone surgery for malignancies of the prostate or urinary bladder. The expression and distribution of the cGKI (isoforms alpha und beta = cGKIα, cGKIß) and the cyclic AMP PDE4 (isoforms PDE4A, 4B, 4C and 4D) were evaluated using specific antibodies in tissue sections (8 - 10 µm) by means of single and double-labelling techniques. RESULTS: In the smooth muscle (SM) portion of the TZ, abundant immunosignals specific for cGKIα and cGKIß were seen. These signals were colocalised with the cyclic nucleotide cyclic GMP and also the PDE5. In the cGK-positive SM and glandular tissue, the presence of the PDE 4A and 4C was observed. PDE4 was also seen colocalised with the cyclic AMP-binding protein kinase (cAK). In addition, PDE4A was detected in varicose nerve fibres transversing the tissue sections, some of these nerves presented staining related to the neuropeptide vasoactive intestinal polypeptide (VIP). Signals related to PDE4B and 4D were more prominent in the stromal smooth musculature than in the glandular epithelial multilayer. CONCLUSIONS: The results are in support of the hypothesis that, in the human prostate, the cyclic GMP- and cyclic AMP-dependent signal transduction systems may synergistically work together. Targeting the cyclic AMP signalling might represent a new option to treat lower urinary tract symptomatology (LUTS) secondary to benign prostatic hyperplasia (BPH).