Immunohistochemical Distribution of Cyclic GMP-Dependent Protein Kinase-1 in Human Prostate Tissue

ObjectivesPhosphodiesterase 5 (PDE5) inhibitors improve smooth muscle relaxation and therefore are considered for pharmacotherapy of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). Cyclic guanosine monophosphate (cGMP)-dependent protein kinase-1 (cGKI) has been identified as one of the downstream targets for cGMP. The aim of the present study was to evaluate, by means of immunohistochemistry and Western blot analysis, the expression and localization of cGKI isoforms in relation to smooth muscle α-actin and cGMP in the human prostate.MethodsCryostat sections of tissue segments excised from the transition zone of human prostates from 11 patients (aged 54–68 yr) were incubated with primary antibodies directed against smooth muscle α-actin, cGMP, cGKI, cGKIα, and cGKIβ. Visualization of double-labelled immunofluorescent staining was achieved by laser microscopy. Western blot analysis was performed to confirm the expression of cGKI isoforms.ResultsImmunoreactivities specific for cGKI, cGKIα, and cGKIβ were observed in the smooth musculature of the transition zone. Double-staining revealed the colocalization of smooth muscle α-actin, cGMP, and cGKI isoforms in smooth muscle cells of the fibromuscular stroma. The expression of cGKI isoforms was confirmed by Western blot analysis.ConclusionsOur results confirm the presence of cGKI isoforms α and β in the transition zone of human prostate tissue. In addition, the colocalization of α-actin, cGMP, and cGKI isoforms provides further evidence for a significant role of the nitric oxide/cGMP pathway in the regulation of smooth muscle contractility in human prostate tissue and therefore could provide additional targets for pharmacotherapy of BPH and LUTS.