title: 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.
abstract: OBJECTIVE
  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.
  
  
  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 microM.
  
  
  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 microM. 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.
authors.affiliation: Department of Urology, Hannover Medical School and IPF PharmaCeuticals, Hannover, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Küthe
authors.forename: Manfred
authors.initials: M
authors.lastname: Reinecke
authors.forename: Stefan
authors.initials: S
authors.lastname: Uckert
authors.forename: Armin
authors.initials: A
authors.lastname: Becker
authors.forename: Ivana
authors.initials: I
authors.lastname: David
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Heitland
authors.forename: Christian G
authors.initials: CG
authors.lastname: Stief
authors.forename: Wolf-Georg
authors.initials: WG
authors.lastname: Forssmann
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Mägert
mesh_terms: D006162:Guanylate Cyclase / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020098:Natriuretic Peptide, C-Type / Q000502:physiology*; D010410:Penile Erection / Q000502:physiology*; D010413:Penis / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D017461:Receptors, Atrial Natriuretic Factor / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D000099242:Atrial Natriuretic Factor Receptor B
chemical_list: D006162:Guanylate Cyclase; D020098:Natriuretic Peptide, C-Type; D012333:RNA, Messenger; D017461:Receptors, Atrial Natriuretic Factor; D000099242:Atrial Natriuretic Factor Receptor B