Uckert Stefan, Stief Christian G, Mayer Margit, Jonas Udo, Hedlund Petter
Department of Urology, Hannover Medical School, 30625, Hannover, Germany.
World J Urol. 2005 Dec;23(6):368-73. doi: 10.1007/s00345-005-0017-3. Epub 2005 Dec 6.
To date, it is widely accepted that several disorders of the male and female urogenital tract, such as erectile dysfunction, bladder overactivity, urinary stone disease and the benign prostatic syndrome, can be therapeutically approached by influencing the function of the smooth musculature of the respective organs. In order to achieve a pronounced drug effect without significant adverse events, especially on the cardiovascular system, a certain degree of tissue selectivity is mandatory. Selective intervention in intracellular pathways regulating smooth muscle tone has become a promising strategy to modulate tissue function. Since the concept of taking a pill as a cure for an illness or the relief of symptoms has become widely accepted by the consumers, the pharmacological treatment of urological diseases has focused on selective, orally available drugs, acting via influencing intracellular regulatory mechanisms, thus combining a high response rate and the advantage of an on-demand intake. PDEs play a central role in controlling the levels of cyclic nucleotides (i.e. cAMP and/or cGMP), which are important second messengers in many transmitter pathways involved in the regulation of biological processes of urogenital tissues. Specifically, the use of isoenzyme selective phosphodiesterase (PDE) inhibitors offers great hope in the medical treatment of various genitourinary diseases. These agents are regarded efficacious, having a fast onset of drug action in the target tissue and an improved effect-to-side-effect ratio. The growing experience with the use of this class of compounds in urology is mainly based on basic research efforts and this field will remain the most exciting and innovative subject in genitourinary physiology and pharmacology for the next few years. These tremendous research efforts may lead to a vast pharmacological armamentarium of possible new treatment options. The purpose of this review is to summarize the current knowledge on the distribution and potential functional significance of PDE isoenzymes in the human lower urinary tract.
迄今为止，人们普遍认为，男性和女性泌尿生殖道的几种疾病，如勃起功能障碍、膀胱过度活动症、尿路结石病和良性前列腺综合征，可以通过影响相应器官平滑肌的功能来进行治疗。为了在不产生明显不良事件的情况下获得显著的药物效果，尤其是对心血管系统的影响，一定程度的组织选择性是必不可少的。对调节平滑肌张力的细胞内途径进行选择性干预已成为调节组织功能的一种有前景的策略。由于服用药物治疗疾病或缓解症状的观念已被消费者广泛接受，泌尿外科疾病的药物治疗一直侧重于选择性的、口服可用的药物，通过影响细胞内调节机制发挥作用，从而兼具高反应率和按需服用的优势。磷酸二酯酶（PDEs）在控制环核苷酸（即cAMP和/或cGMP）水平方面起着核心作用，而环核苷酸是许多参与泌尿生殖组织生物过程调节的递质途径中的重要第二信使。具体而言，使用同工酶选择性磷酸二酯酶（PDE）抑制剂在各种泌尿生殖系统疾病的医学治疗中带来了巨大希望。这些药物被认为是有效的，在靶组织中药物作用起效快，且疗效与副作用比有所改善。在泌尿外科使用这类化合物的经验不断积累，这主要基于基础研究工作，并且在未来几年，该领域仍将是泌尿生殖生理学和药理学中最令人兴奋和创新的课题。这些巨大的研究努力可能会带来大量可能的新治疗选择的药理学武器库。本综述的目的是总结目前关于PDE同工酶在人类下尿路中的分布及其潜在功能意义的知识。
