222 EXPRESSION AND DISTRIBUTION OF PHOSPHODIESTERASE (PDE) ISOENZYMES IN THE HUMAN URETHRA

Abstract

You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology1 Apr 2011222 EXPRESSION AND DISTRIBUTION OF PHOSPHODIESTERASE (PDE) ISOENZYMES IN THE HUMAN URETHRA George Kedia, Markus Kuczyk, Petter Hedlund, and Stefan Ückert George KediaGeorge Kedia Hannover, Germany More articles by this author , Markus KuczykMarkus Kuczyk Hannover, Germany More articles by this author , Petter HedlundPetter Hedlund Lund, Sweden More articles by this author , and Stefan ÜckertStefan Ückert Hannover, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.332AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Up untill today, only a very few studies have addressed the physiology/pharmacology of the human urethra (Hassouna M. et al., J. Urol. 129: 1262–1264, 1983; Abdel-Hakim A. et al., J. Urol. 130: 988–991, 1983; Werkström V. et al., BJU Int. 98: 414–423, 2006). 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. METHODS Using conventional immunohistochemistry (double-labelling technique, laser fluorescence microscopy), thin sections (8 μm – 10 μm) of the human male urethra were exposed to anti-PDE1A, -PDE2A, -PDE3A, -PDE4A, -PDE4B, -PDE5A, anti-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, calcium/calmodulin-dependent), PDE4A, PDE4B (cyclic AMP PDEs) and PDE5A (cyclic GMP PDE) were registered. 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 CGRP. No immunoreactivities specific for PDE2A or PDE3A were detected. 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. This might be of importance with regard to the identification of new pharmacological avenues to facilitate the contraction and relaxation of the human outflow region. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e91 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information George Kedia Hannover, Germany More articles by this author Markus Kuczyk Hannover, Germany More articles by this author Petter Hedlund Lund, Sweden More articles by this author Stefan Ückert Hannover, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...