8-(4-azidophenacyl)thio-cyclic-gmp and zaprinast

This study investigates the effect of protein kinase G (PKG) activation upon proliferation of human cultured prostatic stromal cells. The PKG II activator (8-pCPT-cGMP; IC50 of 113+/-42 nM) and the phosphodiesterase inhibitor, zaprinast (up to 50 microM), but not the PKG I isoform activators (APT-cGMP and PET-cGMP), reduced foetal calf serum-stimulated proliferation. The effect of 8-pCPT-cGMP (30 microM) was blocked by Rp-8-Br-cGMPS (5 microM) and Rp-8-pCPT-cGMP (5 microM), but not Rp-cAMPS (5 microM). 8-pCPT-cGMP (30 microM) and zaprinast (50 microM), but not PET-cGMP (30 microM), caused a significant increase in atypical nuclei and an increase in annexin-V staining. These data indicate that activation of PKG II induces apoptosis of human cultured prostatic stromal cells.

Topics: Aged; Apoptosis; Azides; Cell Division; Cell Nucleus; Cells, Cultured; Cyclic AMP; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Enzyme Inhibitors; Humans; Isoenzymes; Male; Phosphoric Diester Hydrolases; Prostate; Prostatic Hyperplasia; Purinones; Serum; Stromal Cells; Thionucleotides