Protein kinase G II-mediated proliferative effects in human cultured prostatic stromal cells.
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.
Cook
Anna-Louise M
AL
Department of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Melbourne, Victoria 3052, Australia. anna.cook@vcp.monash.edu.au
Haynes
John M
JM
D000368:Aged; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001386:Azides / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002467:Cell Nucleus / Q000502:physiology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011467:Prostate / Q000201:enzymology* / Q000502:physiology; D011470:Prostatic Hyperplasia / Q000201:enzymology / Q000503:physiopathology; D011688:Purinones / Q000494:pharmacology; D044967:Serum / Q000378:metabolism; D017154:Stromal Cells / Q000201:enzymology* / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology
C090860:8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphorothioate; D001386:Azides; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D011688:Purinones; D013873:Thionucleotides; C081534:8-(4-azidophenacyl)thio-cyclic GMP; C083763:8-bromoguanosino-3',5'-cyclic monophosphorothioate; C016957:adenosine-3',5'-cyclic phosphorothioate; C055656:8-((4-chlorophenyl)thio)cyclic-3',5'-GMP; D000242:Cyclic AMP; D017869:Cyclic GMP-Dependent Protein Kinases; D010727:Phosphoric Diester Hydrolases; C011145:zaprinast; D006152:Cyclic GMP