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

Author

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

Summary, in English

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) alpha isoform has been linked to erectile dysfunction and diabetes mellitus. So far, the expression of cGKI alpha and beta isoforms has not been evaluated in human penile erectile tissue. To evaluate the expression of cGKI alpha and beta isoforms in relation to smooth muscle alpha-actin, cGMP, and endothelial NO synthase (eNOS) in human cavernous arteries (HCAs) and human corpus cavernosum (HCC). Cryostat sections of HCA and HCC were incubated with primary antibodies directed against alpha-actin, cGMP, eNOS, cGKI, cGKI alpha, and cGKI beta. 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. Expression of cGKI alpha and beta isoforms in relation to smooth muscle alpha-actin, cGMP, and eNOS in human penile erectile tissue. Immunoreactivities specific for cGKI, cGKI alpha, and cGKI beta 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. Our results demonstrate, for the first time, the expression of both cGKI alpha and beta isoforms in the smooth musculature of HCA and HCC. Corresponding to recent findings from animal studies, the presence of cGKI alpha and beta provides further evidence for a significant role of these enzymes in the control of smooth muscle function in human penile erectile tissue.

Publishing year

2008

Language

English

Pages

536-543

Publication/Series

Journal of Sexual Medicine

Volume

5

Issue

3

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Obstetrics, Gynecology and Reproductive Medicine

Keywords

  • cavernosum
  • corpus
  • cavernous arteries
  • cyclic gmp
  • erectile dysfunction
  • nitric oxide
  • protein kinase G

Status

Published

ISBN/ISSN/Other

  • ISSN: 1743-6109