Märker Dr. Viktoria, Ueckert Prof. Stefan, Waldkirch Priv-Doz. Eginhard, Hedlund Prof. Petter

(188) ISOFORMS OF THE CYCLIC GMP-DEPENDENT PROTEIN KINASE ARE EXPRESSED IN HUMAN PENILE ERECTILE TISSUE

  • Urology
  • Reproductive Medicine
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Psychiatry and Mental health

Abstract Objectives Aside from the activity of the gaseous transmitter molecule nitric oxide (NO) and the cyclic GMP producing enzyme soluble guanylyl cyclase (sGC) in human penile erectile tissue, intracellular receptor proteins activated by the binding of cyclic GMP have been considered to play a significant role in the erection process. In animal models, a down-regulation of the cyclic GMP-dependent/binding protein kinase I (cGKI) has been linked to the on-set of diabetes mellitus and erectile dysfunction (ED). Our study aimed to investigate in human penile erectile tissue (corpus cavernosum and cavernous arteries) the expression of cGKI (isoforms alpha and beta) in relation to smooth muscle alpha-actin, cyclic GMP and the endothelial nitric oxide synthase (eNOS). Methods Cryostat sections of human penile erectile tissue were exposed to primary antibodies (ABs) directed against alpha-actin, cGKI, cGKI alpha and cGKI beta, cyclic GMP and eNOS, followed by the incubation with fluorochrome-labeled secondary ABs. Visualization was commenced by means of laser fluorescence microscopy. Western blot analysis was also performed. Results Abundant immunoreactivities indicating the presence of cGKI alpha and beta and the second messenger cyclic cGMP were observed in the trabecular smooth musculature as well as in the smooth muscle layer of tiny cavernous arteries. Double staining revealed the co-localization of cGKI and eNOS within the endothelium of small arterial vessels. The expression of cGKI alpha and beta was confirmed by Western blot analysis. Conclusions Theclose relation of isoforms of the cGKI to key mediators of the NO pathway (eNOS, cyclic GMP), as demonstrated by conventional immunohistochemistry, provides further evidence for a significant role of cyclic GMP-binding intracellular function proteins in the control of vascular and non-vascular penile erectile smooth muscle. Conflicts of Interest no conflict of interest.

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