title: Endogenous vasoactive peptides and the human vagina--a molecular biology and functional study.
abstract: BACKGROUND
  Endogenous peptides, such as vasoactive intestinal polypeptide (VIP), C-type natriuretic peptide (CNP), and bradykinin (BK), have been proposed to play a role in the female sexual arousal response by exerting relaxation of clitoral, labial, and vaginal smooth muscle. While the effects of endogenous peptides on the human male erectile tissue have already been described, only very few studies have been conducted to investigate the peptidergic control of female genital tissues, including the vagina.
  
  
  OBJECTIVE
  To elucidate the expression of mRNA specifically encoding for peptide receptors in the human vagina and the effects of VIP, CNP, and BK on the tension induced by endothelin-1 (ET-1) of isolated human vaginal wall smooth muscle. The production of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in response to exposure of the tissue to the peptides was also measured.
  
  
  METHODS
  The expression of mRNA encoding for receptor proteins specific for VIP, CNP, and BK were investigated by means of molecular biology (reverse transcriptase polymerase chain reaction [RT-PCR] analysis). Using the organ bath technique, the effects of VIP, CNP, and BK (0.1 nM to 1 µM) on the tension induced by 0.1 µM ET-1 of human vaginal strips were investigated. The tissue was also exposed to three different concentrations of VIP, CNP, and BK (0.01 µM, 0.1 µM, 1 µM) and the production of cAMP and cGMP determined by means of radioimmunoassays.
  
  
  METHODS
  Characterize the expression of peptide receptors in the human vagina and measure the relaxation exerted by BK, CNP, and VIP on the contraction induced by ET-1 of isolated human vaginal tissue. In addition, the effects of the peptides on the production of cAMP and cGMP were also elucidated.
  
  
  RESULTS
  RT-PCR analysis revealed the expression of mRNA transcripts encoding for the VIP receptors VIP1R/vasoactive intestinal polypeptide receptor type 1 (VPAC1) and VIP2R/VPAC2, CNP receptors natriuretic peptide receptor type A (NPRA), natriuretic peptide receptor type B (NPRB) and natriuretic peptide receptor type C (NPRC), and BK receptor B2R. The tension induced by ET-1 was reversed by the peptides with the following rank order of efficacy: BK (21.7%) > VIP (20.9%) > CNP (13.3%). The relaxing effects of VIP and BK were paralleled by a 4.8-fold and fivefold increase in cAMP, while the production of cGMP was stimulated 38-fold and 119-fold in the presence of CNP or BK, respectively.
  
  
  CONCLUSIONS
  Our results are in support of the hypothesis that endogenous peptides may contribute to the control of human vaginal smooth muscle tone through the involvement of the cyclic nucleotide-dependent pathways.
authors.affiliation: Department of Urology & Urological Oncology, Division of Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Harrina E
authors.initials: HE
authors.lastname: Rahardjo
authors.forename: Andreas
authors.initials: A
authors.lastname: Brauer
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Mägert
authors.forename: Markus
authors.initials: M
authors.lastname: Meyer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kauffels
authors.forename: Akmal
authors.initials: A
authors.lastname: Taher
authors.forename: Djoko
authors.initials: D
authors.lastname: Rahardjo
authors.forename: Udo
authors.initials: U
authors.lastname: Jonas
authors.forename: Markus A
authors.initials: MA
authors.lastname: Kuczyk
authors.forename: Stefan
authors.initials: S
authors.lastname: Uckert
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001920:Bradykinin / Q000378:metabolism*; D019332:Endothelin-1 / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism*; D009712:Nucleotides, Cyclic / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism; D015398:Signal Transduction; D014621:Vagina / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
chemical_list: D019332:Endothelin-1; D009712:Nucleotides, Cyclic; D012333:RNA, Messenger; D018000:Receptors, Peptide; D020098:Natriuretic Peptide, C-Type; D014660:Vasoactive Intestinal Peptide; D001920:Bradykinin