739 Phosphodiesterase isoenzymes in the human urethra: Relation to neuronal nitric oxide synthase-, VIP- and CGRP-containing nerves

739 - Phosphodiesterase isoenzymes in the human urethra: Relation to neuronal nitric oxi... Page 1 of 2

e739 Phosphodiesterase isoenzymes in the human urethra: Relation to neuronal nitric oxide synthase-, VIP- and CGRP-containing nerves 1

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Kedia G.T. , Ückert S. , Oelke M. , Kuczyk M.A. , Hedlund P. 1

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Hanover Medical School, Division of Surgery, Dept. of Urology & 2

Urological Oncology, Hanover, Germany, University Vita Salute San Raffaele, Urological Research Institute (URI), Milan, Italy INTRODUCTION & OBJECTIVES: Up until today, a few studies only have addressed the physiology/pharmacology of the human urethra. An involvement of the nitric oxide (NO)/cyclic GMP pathway in mediating the relaxation of the bladder outlet and urethra during the micturition phase has been supposed. The present study aimed to evaluate in the human male urethra by means of immunohistochemistry the expression and distribution of cyclic AMP and cyclic GMP phosphodiesterase (PDE) isoenzymes in relation to key mediators/proteins of the cyclic GMP and cyclic AMP pathways. MATERIAL & METHODS: Using conventional immunohistochemistry (double-labelling technique, laser fluorescence microscopy), thin sections (8 µm to 10 µm) of the human male urethra were exposed to anti-PDE1A, -PDE2A, -PDE3A, -PDE4A, -PDE4B, -PDE5A, -nNOS (neuronal nitric oxide synthase), -VIP (vasoactive intestinal polypeptide) and -CGRP (calcitonin gene-related peptide) antibodies followed by the application of fluorochrome-labelled secondary antibodies. RESULTS: In the smooth muscle (SM) portion of the urethra, immunosignals specific for PDE1A (cyclic AMP/cyclic GMP PDE, 2+

Ca /calmodulin-dependent), PDE4A, PDE4B (cyclic AMP PDEs) and PDE5A (cyclic GMP PDE) were registered. No immunoreactivities specific for PDE2A or PDE3A were observed. SM bundles were seen innervated by varicose nerve fibers characterized by the expression of nNOS. Some of these nerves also presented staining related to VIP or

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4/7/2012

739 - Phosphodiesterase isoenzymes in the human urethra: Relation to neuronal nitric oxi... Page 2 of 2

e739a CGRP. The neuronal structures appeared free of immunosignals specific for any PDE protein. CONCLUSIONS: PDE isoenzymes type 1A, 4A, 4B and 5A are expressed in human urethral smooth muscle. The findings implicate that the cyclic AMP and cyclic GMP pathways work synergistically together in the control of urethral smooth muscle function.

file://F:\RamShankar\April\04-05-12\Cip\Sour\739.html

4/7/2012