Expression of Guanylyl Cyclase B in the Human Corpus Cavernosum Penis and the Possible Involvement of its Ligand C-type Natriuretic Polypeptide in the Induction of Penile Erection
2003; Lippincott Williams & Wilkins; Volume: 169; Issue: 5 Linguagem: Inglês
10.1097/01.ju.0000055602.35858.8f
ISSN1527-3792
AutoresAndrea Küthe, M. Reinecke, Stefan Ückert, Armin Becker, I. David, Aleksandra Heitland, Christian G. Stief, Wolf‐Georg Forssmann, Hans‐Jürgen Mägert,
Tópico(s)Coagulation, Bradykinin, Polyphosphates, and Angioedema
ResumoNo AccessJournal of UrologyINVESTIGATIVE UROLOGY1 May 2003Expression of Guanylyl Cyclase B in the Human Corpus Cavernosum Penis and the Possible Involvement of its Ligand C-type Natriuretic Polypeptide in the Induction of Penile Erection ANDREA KÜTHE, MANFRED REINECKE, STEFAN ÜCKERT, ARMIN BECKER, IVANA DAVID, ALEKSANDRA HEITLAND, CHRISTIAN G. STIEF, WOLF-GEORG FORSSMANN, and HANS-JÜRGEN MÄGERT ANDREA KÜTHEANDREA KÜTHE , MANFRED REINECKEMANFRED REINECKE , STEFAN ÜCKERTSTEFAN ÜCKERT , ARMIN BECKERARMIN BECKER , IVANA DAVIDIVANA DAVID , ALEKSANDRA HEITLANDALEKSANDRA HEITLAND , CHRISTIAN G. STIEFCHRISTIAN G. STIEF , WOLF-GEORG FORSSMANNWOLF-GEORG FORSSMANN , and HANS-JÜRGEN MÄGERTHANS-JÜRGEN MÄGERT View All Author Informationhttps://doi.org/10.1097/01.ju.0000055602.35858.8fAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The induction of penile erection depends on the depletion of free intracellular Ca2+ from the cytosol into the sarcoplasmic reticulum of smooth muscle cells of the corpus cavernosum. This process is regulated by a complex system of signal transduction pathways. In this context guanylyl and adenylyl cyclases as well as cyclic nucleotide monophosphate degrading phosphodiesterases have essential roles and represent important target molecules for the development of drugs for erectile dysfunction. Sildenafil, which is an inhibitor of phosphodiesterase 5, is frequently used for this application but, unfortunately, it has undesirable side effects. Therefore, we investigated the suitability of membrane bound guanylyl cyclases as alternative target proteins. Materials and Methods: We determined mRNA transcripts specific for guanylyl cyclase B, a receptor of the peptide hormone C-type natriuretic polypeptide, in human corpus cavernosum. We performed immunohistochemistry to evaluate the presence of guanylyl cyclase B in corpus cavernosum and helical artery smooth muscle cells. We further investigated whether C-type natriuretic polypeptide increases intracellular cyclic guanosine monophosphate and performed organ bath studies using corpus cavernosum muscle strips and C-type natriuretic polypeptide at concentrations of 1 to 1 μM. Results: mRNA transcripts were detected encoding for guanylyl cyclase-B, a receptor of the peptide hormone C-type natriuretic polypeptide, in human corpus cavernosum. This finding was verified at the protein level by immunohistochemistry that demonstrated guanylyl cyclase B in corpus cavernosum and helical artery smooth muscle cells. We further noted that C-type natriuretic polypeptide increased intracellular cyclic guanosine monophosphate. In organ bath studies with corpus cavernosum muscle strips C-type natriuretic polypeptide at concentrations of 1 to 1 μM. led to smooth muscle relaxation from 5% to 40%. Conclusions: The results indicate a role for C-type natriuretic polypeptide and its receptor in the induction of penile erection and its possible future therapeutic use for erectile dysfunction. References 1 : The molecular biology of cyclic nucleotide phosphodiesterases. Prog Nucleic Acid Res Mol Biol1999; 63: 1. Google Scholar 2 : Signal transduction in cavernous smooth muscle. World J Urol1997; 15: 27. Google Scholar 3 : Sildenafil, a novel effective oral therapy for male erectile dysfunction. Br J Urol1996; 78: 257. 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Google Scholar From the Department of Urology, Hannover Medical School and IPF PharmaCeuticals, Hannover, Germany, and Department of Anatomy, University of Zürich, Zürich, Switzerland© 2003 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 169Issue 5May 2003Page: 1918-1922 Advertisement Copyright & Permissions© 2003 by American Urological Association, Inc.Keywordsguanylate cyclasepenisnatriuretic peptide, C-typepenile erectionmuscle, smoothMetricsAuthor Information ANDREA KÜTHE Equal study contribution. More articles by this author MANFRED REINECKE Equal study contribution. More articles by this author STEFAN ÜCKERT More articles by this author ARMIN BECKER More articles by this author IVANA DAVID More articles by this author ALEKSANDRA HEITLAND More articles by this author CHRISTIAN G. STIEF More articles by this author WOLF-GEORG FORSSMANN More articles by this author HANS-JÜRGEN MÄGERT More articles by this author Expand All Advertisement PDF DownloadLoading ...
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