Polson J B, Strada S J
Department of Pharmacology and Therapeutics, University of South Florida, College of Medicine, Tampa 33612-4799, USA.
Annu Rev Pharmacol Toxicol. 1996;36:403-27. doi: 10.1146/annurev.pa.36.040196.002155.
At least 30 different phosphodiesterase (PDE) enzymes have now been identified in mammalian tissues and cells, many of which are products of separate genes. These different isoenzyme forms can be subdivided into seven families based on their genetic and functional characteristics. Relatively specific inhibitors are available for at least five of these PDE families. A functional classification based on substrate specificity, regulatory properties, and sensitivity to inhibition by isozyme- and tissue-selective inhibitors can be used in describing the PDEs of vascular smooth muscle. Inhibition of these PDEs, especially with inhibitors of the PDE3 isoform, promotes vascular relaxation, particularly if the preparation of smooth muscle has been preconracted. For the most part, the drugs appear to act directly on smooth muscle; their effects are usually observed in endothelium-denuded preparations. In addition to their cardiotonic properties, many PDE3 inhibitors possess antiplatelet and thrombolytic activities, thereby suggesting the potential benefit of these drugs in treating diseases of the cardiovascular system. Isozyme- and cell-specific drugs have been shown to alter the synthetic state (i.e. proliferative phenotype) of smooth muscle cultures toward the appearance of the contractile phenotype. This suggests the possible use of selective PDE inhibitors to minimize the problem of restenosis seen after angioplasty. The development of novel methods to deliver more potent and selective PDE inhibitors to individual cell types and subcellular locales will lead to new therapeutic uses for this class of drugs in diseases of the cardiovascular system.
目前已在哺乳动物组织和细胞中鉴定出至少30种不同的磷酸二酯酶（PDE），其中许多是不同基因的产物。根据其遗传和功能特性，这些不同的同工酶形式可细分为七个家族。至少有五个PDE家族有相对特异性的抑制剂。基于底物特异性、调节特性以及对同工酶和组织选择性抑制剂抑制作用的敏感性的功能分类，可用于描述血管平滑肌中的PDE。抑制这些PDE，尤其是使用PDE3同工型抑制剂，可促进血管舒张，特别是在平滑肌已预先收缩的制剂中。在很大程度上，这些药物似乎直接作用于平滑肌；其作用通常在去除内皮的制剂中观察到。除了具有强心特性外，许多PDE3抑制剂还具有抗血小板和溶栓活性，因此提示这些药物在治疗心血管系统疾病方面可能有益。已证明同工酶和细胞特异性药物可使平滑肌培养物的合成状态（即增殖表型）向收缩表型转变。这表明选择性PDE抑制剂可能用于将血管成形术后出现的再狭窄问题降至最低。开发将更有效和选择性的PDE抑制剂递送至个体细胞类型和亚细胞区域的新方法，将为这类药物在心血管系统疾病中带来新的治疗用途。
