Expression of cAMP-dependent protein kinase isoforms in the human prostate: Functional significance and relation to PDE4

Objectives: To investigate the expression of isoforms of the cyclic AMP (cAMP)dependent protein kinase (cAK) in the transition zone of the human prostate and the functional significance of the enzyme in the control of prostate smooth muscle. Methods: Using Western blot analysis and immunohistochemistry, the expression and distribution in the prostate of cAKIα, cAKIβ, cAKIIα, and cAKIIβ in relation to α-actin and the phosphodiesterase PDE4 (types A and B) were investigated. The effects of the cAK inhibitor Rp-8-CPT-cAMPS on the reversion of the adrenergic tension of isolated prostate tissue induced by forskolin, rolipram, sodium nitroprusside (SNP), and tadalafil were examined by means of the organ bath technique. Results: Immunosignals specific for cAKIα, cAKIIα, and cAKIIβ were observed in the smooth musculature and glandular structures of the prostate. Double stainings revealed the colocalization of α-actin and PDE4 with the cAK isoforms. The expression of the cAK isoforms was confirmed by Western blot analysis. The relaxation of the tension induced by norepinephrine brought about by forskolin, rolipram, SNP, and tadalafil was significantly attenuated by Rp-8-CPT-cAMPS. Conclusions: The colocalization of smooth muscle α-actin and PDE4 with cAK, as well as the results from the organ bath experiments, provide further evidence for a pivotal role of the cAMP-dependent signaling in the regulation of prostate smooth muscle contractility. Compounds interacting with the cAMP/cAK pathway might represent a new therapeutic avenue to treat symptoms of benign prostatic hyperplasia and lower urinary tract symptomatology.