title: Phosphodiesterase type 1, calcitonin gene-related peptide and vasoactive intestinal polypeptide are involved in the control of human vaginal arterial vessels.
abstract: OBJECTIVE
  The vagina makes a major contribution to the normal female sexual response cycle. An increase in vaginal blood flow is considered a key event in the mechanism of sexual arousal. Recent research has focused mainly on the cyclic GMP pathway and phosphodiesterase type 5 (PDE5, cyclic GMP specific PDE) in the control of vaginal vascular smooth muscle, whereas only little is known on the role of other key proteins and mediators of cyclic nucleotide mediated signaling in this process. The aim of the present study was to evaluate in the human vagina, by means of immunohistochemistry, the expression and distribution of phosphodiesterase type 1 (PDE1, known to hydrolize both cyclic AMP and cyclic GMP) in relation to calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and protein gene product 9.5 (PGP 9.5).
  
  
  METHODS
  Sections of human vagina (full wall specimens) were incubated with antibodies directed against PDE1, CGRP, VIP, PGP 9.5 and alpha-actin, followed by exposure to fluorochrome-labelled secondary antibodies. Visualization was commenced by means of laser fluorescence microscopy.
  
  
  RESULTS
  Microscopic examination revealed a dense meshwork of PGP 9.5-positive nerve fibers innervating the sections of vaginal wall. Small vessels interspersing the tissue presented dense staining for PDE1 in their smooth musculature. Blood vessels were seen surrounded by PDE1-immunoreactive longitudinal smooth muscle fibers. The vessels were also found innervated by PGP-positive varicose nerve fibers characterized by the expression of CGRP. Some fibers presented immunosignals specific for VIP.
  
  
  CONCLUSIONS
  Key mediators of the cyclic AMP and cyclic GMP pathways are co-localized in nerves seen in close proximity to vascular smooth muscle expressing PDE1. These findings suggest that both signaling cascades are involved in the control of vaginal blood flow.
authors.affiliation: Hannover Medical School, Division of Surgery, Department of Urology & Urological Oncology, Hannover, Germany. sue_de_99@yahoo.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Uckert
authors.forename: Knut
authors.initials: K
authors.lastname: Albrecht
authors.forename: Markus A
authors.initials: MA
authors.lastname: Kuczyk
authors.forename: Petter
authors.initials: P
authors.lastname: Hedlund
authors.forename: Matthias
authors.initials: M
authors.lastname: Oelke
mesh_terms: D000293:Adolescent; D000328:Adult; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D005260:Female; D006801:Humans; D043264:Phosphodiesterase I / Q000502:physiology*; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*; D014621:Vagina / Q000098:blood supply / Q000201:enzymology / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000502:physiology*; D055815:Young Adult
chemical_list: C482860:UCHL1 protein, human; D014660:Vasoactive Intestinal Peptide; D043264:Phosphodiesterase I; D043222:Ubiquitin Thiolesterase; D015740:Calcitonin Gene-Related Peptide
keywords: Calcitonin gene-related peptide; Human vagina; Immunohistochemistry; Phosphodiesterase type 1; Vascular smooth muscle; Vasoactive intestinal polypeptide