Hannover Medical School, Department of Urology and Uro-Oncology, Hannover, Germany.
Urology. 2010 Aug;76(2):515.e8-14. doi: 10.1016/j.urology.2010.04.035.
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.
Using Western blot analysis and immunohistochemistry, the expression and distribution in the prostate of cAKIalpha, cAKIbeta, cAKIIalpha, and cAKIIbeta in relation to alpha-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.
Immunosignals specific for cAKIalpha, cAKIIalpha, and cAKIIbeta were observed in the smooth musculature and glandular structures of the prostate. Double stainings revealed the colocalization of alpha-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.
The colocalization of smooth muscle alpha-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.
研究环磷酸腺苷（cAMP）依赖性蛋白激酶（cAK）同工型在人前列腺移行区的表达及其在前列腺平滑肌控制中的功能意义。
采用 Western blot 分析和免疫组织化学方法，研究 cAKIalpha、cAKIbeta、cAKIIalpha 和 cAKIIbeta 同工型与α-肌动蛋白和磷酸二酯酶 PDE4（A 型和 B 型）在前列腺中的表达和分布关系。采用器官浴技术，研究 cAK 抑制剂 Rp-8-CPT-cAMPS 对福司柯林、罗利普兰、硝普钠（SNP）和他达拉非诱导的离体前列腺组织肾上腺素张力恢复的影响。
在前列腺的平滑肌和腺结构中观察到针对 cAKIalpha、cAKIIalpha 和 cAKIIbeta 的特异性免疫信号。双染色显示α-肌动蛋白和 PDE4 与 cAK 同工型的共定位。Western blot 分析证实了 cAK 同工型的表达。福司柯林、罗利普兰、SNP 和他达拉非引起的去甲肾上腺素诱导的张力松弛被 Rp-8-CPT-cAMPS 显著减弱。
平滑肌α-肌动蛋白和 PDE4 与 cAK 的共定位以及器官浴实验的结果进一步提供了证据，证明 cAMP 依赖性信号在调节前列腺平滑肌收缩性方面起着关键作用。与 cAMP/cAK 途径相互作用的化合物可能代表治疗良性前列腺增生和下尿路症状的新治疗途径。
