Expression and distribution of cyclic AMP- and cyclic GMP-binding protein kinases in the human vagina- an immunohistochemical study.

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

Division of Surgery, Department of Urology and Uro-Oncology, Hannover Medical School, Hannover 30625, Germany. streetgang@gmx.de

The journal of sexual medicine 2010 Feb

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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. 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. Expression and distribution of cAK and cGKI(alpha,beta) in relation to eNOS, VIP, and PGP 9.5 in human vaginal tissue. Immunohistochemical techniques were applied to sections of human vaginal full wall specimens in order to evaluate the presence of cAK and cGKI(alpha,beta) 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. Immunostaining specific for cGKIbeta was observed in vascular and nonvascular smooth muscle of the vagina. In the endothelial layer, cGKIbeta was found colocalized with eNOS. In contrast, no signals indicating cGKIalpha 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 cGKIbeta was confirmed by Western blotting. Our results demonstrate the expression of cAK and cGKIbeta 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.

Citation

Stefan Uckert, Eginhard S Waldkirch, Knut Albrecht, Julia Sonnenberg, Kristina Langnäse, Karin Richter, Petter Hedlund, Markus A Kuczyk. Expression and distribution of cyclic AMP- and cyclic GMP-binding protein kinases in the human vagina- an immunohistochemical study. The journal of sexual medicine. 2010 Feb;7(2 Pt 2):888-95