Expression and distribution of cyclic AMP- and cyclic GMP-binding protein kinases in the human vagina - An Immunohistochemical study

Stefan Ückert, Eginhard S. Waldkirch, Knut Albrecht, Julia Sonnenberg, Kristina Langnäse, Karin Richter, Petter Hedlund, Markus A. Kuczyk

Research output: Contribution to journalArticlepeer-review


Introduction: In contrast to research findings describing the localization of nitric oxide synthases (NOS), guanylyl cyclases, and cyclic adenosine monophosphate (cAMP)- and cyclic guanosine monophosphate (cGMP)-degrading phosphodiesterase isoenzymes in the human vagina, the distribution of proteins known as major targets for cyclic nucleotides has not yet been evaluated. cAMP- and cGMP-dependent protein kinases (cAK, cGKI) have been identified as important receptors for cyclic nucleotides downstream the signaling cascades. Aim.: To investigate, by means of immunohistochemistry, the expression of cAK and cGKI in relation to endothelial NOS (eNOS), vasoactive intestinal polypeptide (VIP), and protein gene product 9.5 (PGP 9.5) in the human vagina. Main Outcome Measures.: Expression and distribution of cAK and cGKI(α,β) in relation to eNOS, VIP, and PGP 9.5 in human vaginal tissue. Methods.: Immunohistochemical techniques were applied to sections of human vaginal full wall specimens in order to evaluate the presence of cAK and cGKI(α,β) in relation to VIP, PGP 9.5, and eNOS, respectively. Western blot analyses were conducted using cytosolic supernatants of homogenized specimens of the vaginal wall and epithelium. Results.: Immunostaining specific for cGKIβ was observed in vascular and nonvascular smooth muscle of the vagina. In the endothelial layer, cGKIβ was found colocalized with eNOS. In contrast, no signals indicating cGKIα were registered. cAK-positive subepithelial vessels were found to be innervated by a dense meshwork of PGP-containing varicose nerve fibers, some of which presented expression of VIP. The expression of cAK and cGKIβ was confirmed by Western blotting. Conclusions.: Our results demonstrate the expression of cAK and cGKIβ in the human vagina. The colocalization with VIP and eNOS underlines the significance of both the cAMP and GMP pathway in the control of human vaginal vascular and nonvascular smooth muscle.

Original languageEnglish
Pages (from-to)888-895
Number of pages8
JournalJournal of Sexual Medicine
Issue number2 PART 2
Publication statusPublished - 2010


  • Cyclic AMP
  • Cyclic GMP
  • Immunohistochemistry
  • Protein kinases
  • Vaginal physiology

ASJC Scopus subject areas

  • Urology
  • Obstetrics and Gynaecology
  • Reproductive Medicine
  • Medicine(all)

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