Immunohistochemical distribution of cyclic GMP-dependent protein kinase-1 in human prostate tissue.
OBJECTIVE
Phosphodiesterase 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 alpha-actin and cGMP in the human prostate.


METHODS
Cryostat 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 alpha-actin, cGMP, cGKI, cGKIalpha, and cGKIbeta. Visualization of double-labelled immunofluorescent staining was achieved by laser microscopy. Western blot analysis was performed to confirm the expression of cGKI isoforms.


RESULTS
Immunoreactivities specific for cGKI, cGKIalpha, and cGKIbeta were observed in the smooth musculature of the transition zone. Double-staining revealed the colocalization of smooth muscle alpha-actin, cGMP, and cGKI isoforms in smooth muscle cells of the fibromuscular stroma. The expression of cGKI isoforms was confirmed by Western blot analysis.


CONCLUSIONS
Our results confirm the presence of cGKI isoforms alpha and beta in the transition zone of human prostate tissue. In addition, the colocalization of alpha-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.
Waldkirch
Eginhard S
ES
Hannover Medical School, Department of Urology, 30625 Hannover, Germany. waldkirch.eginhard@mh-hannover.de
Uckert
Stefan
S
Langnäse
Kristina
K
Richter
Karin
K
Jonas
Udo
U
Wolf
Gerald
G
Andersson
Karl-Erik
KE
Stief
Christian G
CG
Hedlund
Petter
P
D000199:Actins / Q000378:metabolism; D000368:Aged; D015153:Blotting, Western; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000201:enzymology*; D011471:Prostatic Neoplasms / Q000201:enzymology*
D000199:Actins; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP