Expression and distribution of cyclic GMP-dependent protein kinase-1 isoforms in human penile erectile tissue

Eginhard Waldkirch, Stefan Uckert, Katja Sigl, Florian Imkamp, Kristina Langnaese, Karin Richter, Udo Jonas, Michael Sohn, Christian Stief, Gerald Wolf, Petter Hedlund

Research output: Contribution to journalArticle

Abstract

Introduction. Besides the bioavailability of nitric oxide (NO), downstream guanine monophosphate (cGMP) effector proteins are also considered to play a significant role in penile vascular disease. In animal studies, a downregulation of the cGMP-dependent protein kinase-1 (cGKI) α isoform has been linked to erectile dysfunction and diabetes mellitus. So far, the expression of cGKI α and β isoforms has not been evaluated in human penile erectile tissue. Aim. To evaluate the expression of cGKI α and β isoforms in relation to smooth muscle α-actin, cGMP, and endothelial NO synthase (eNOS) in human cavernous arteries (HCAs) and human corpus cavernosum (HCC). Methods. Cryostat sections of HCA and HCC were incubated with primary antibodies directed against α-actin, cGMP, eNOS, cGKI, cGKI α, and cGKI β. Visualization of double-labeled immunofluorescent stainings was achieved by laser microscopy. Western blot analysis was performed in order to confirm the expression of cGKI isoforms. Main Outcome Measures. Expression of cGKI α and β isoforms in relation to smooth muscle α-actin, cGMP, and eNOS in human penile erectile tissue. Results. Immunoreactivities specific for cGKI, cGKI α, and cGKI β were observed within the smooth musculature and the endothelium of cavernous arteries and sinusoids. Double stainings revealed the colocalization of alpha-actin, cGMP, eNOS, and cGKI isoforms. The expression of cGKI isoforms was confirmed by Western blot analysis. Conclusions. Our results demonstrate, for the first time, the expression of both cGKI α and β isoforms in the smooth musculature of HCA and HCC. Corresponding to recent findings from animal studies, the presence of cGKI α and β provides further evidence for a significant role of these enzymes in the control of smooth muscle function in human penile erectile tissue.

Original languageEnglish
Pages (from-to)536-543
Number of pages8
JournalJournal of Sexual Medicine
Volume5
Issue number3
DOIs
Publication statusPublished - Mar 2008

Keywords

  • Cavernous arteries
  • Corpus cavernosum
  • Cyclic GMP
  • Erectile dysfunction
  • Nitric oxide
  • Protein kinase G

ASJC Scopus subject areas

  • Urology
  • Obstetrics and Gynaecology

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    Waldkirch, E., Uckert, S., Sigl, K., Imkamp, F., Langnaese, K., Richter, K., Jonas, U., Sohn, M., Stief, C., Wolf, G., & Hedlund, P. (2008). Expression and distribution of cyclic GMP-dependent protein kinase-1 isoforms in human penile erectile tissue. Journal of Sexual Medicine, 5(3), 536-543. https://doi.org/10.1111/j.1743-6109.2007.00735.x