title: Protein kinase enzymes in the human vagina-relation to key mediators of the cyclic AMP and cyclic GMP pathways.
abstract: Aside from phosphodiesterase (PDE) isoenzymes, protein kinases (cAK=cyclic AMP-binding protein kinase, cGK=cyclic GMP-binding protein kinase) have also been identified as important receptors for cyclic nucleotides. A significance of protein kinases in the control of the function of the male and female reproductive tract has been suggested; however, up until today, only a few approaches have addressed these enzymes in female genital tissues. The present study aimed to investigate by means of biochemical and immunohistochemical methods the expression of cAK and cGK. The distribution of cAK(I) and cGK(I) in relation to the vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and PDE type 4 (PDE4) was also evaluated. Cytosolic supernatants prepared from specimens of vaginal wall smooth muscle or epithelium were subjected to anion exchange chromatography and the activities of cAK and cGK(I) measured. To evaluate the distribution of cAK(I) and cGK(I) in relation to VIP, CGRP and PDE4, immunohistochemistry was conducted in sections of the human vaginal wall (full-wall specimens). Activities representing cGK(I) and cAK(I) were resolved from the chromatography column. Staining specific for cAK(Iα) was identified in both vascular and non-vascular vaginal smooth musculature, immunoreactivity for cGK(Iβ) was observed in the smooth muscle and endothelium of small arteries interspersing the sections. cAK(Iα)-positive vessels were found innervated by slender varicose nerve fibers presenting the expression of VIP and CGRP. These arteries also expressed PDE4. Localization of cAK and cGK in close relation to key mediators of the cyclic AMP (PDE4, VIP) and cyclic GMP (CGRP) pathways indicate that both signaling systems may synergistically work together in human vaginal tissue.
authors.affiliation: Department of Urology and Urological Oncology, Division of Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Ückert
authors.affiliation: Department of Urology and Urological Oncology, Division of Surgery, Hannover Medical School, Hannover, Germany.|Institute for Biochemical Research and Analysis, Sexual Function Research Unit, Barsinghausen am Deister, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Sonnenberg
authors.affiliation: Institute for Biochemical Research and Analysis, Sexual Function Research Unit, Barsinghausen am Deister, Germany.
authors.forename: J E
authors.initials: JE
authors.lastname: Sonnenberg
authors.affiliation: Klinikum Hildesheim GmbH, Department of Obstetrics and Gynecology, Hildesheim, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Kauffels
authors.affiliation: Hannover Medical School, Institute for Legal (Forensic) Medicine, Hannover, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Albrecht
authors.affiliation: Department of Urology and Urological Oncology, Division of Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: M A
authors.initials: MA
authors.lastname: Kuczyk
authors.affiliation: Linköping University, Faculty of Medical and Health Sciences, Division of Pharmacology and Drug Research, Linköping, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Hedlund
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D015398:Signal Transduction / Q000502:physiology*; D014621:Vagina / Q000201:enzymology*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D006152:Cyclic GMP; D015740:Calcitonin Gene-Related Peptide