Department of Physiology, University Health Network, Toronto, Ontario, Canada.
Curr Opin Pharmacol. 2011 Dec;11(6):714-9. doi: 10.1016/j.coph.2011.10.017. Epub 2011 Oct 31.
Cyclic nucleotide phosphodiesterases (PDEs) encompass a large group of enzymes that regulate intracellular levels of two-second messengers, cAMP and cGMP, by controlling the rates of their degradation. More than 60 isoforms, subdivided into 11 gene families (PDE1-11), exist in mammals with at least six families (PDE1-5 and PDE8) identified in mammalian hearts. The two predominant families implicated in regulating contraction strength of the heart are PDE3 and PDE4. Studies using transgenic models in combination with family-specific PDE inhibitors have demonstrated that PDE3A, PDE4B, and PDE4D isoforms regulate cardiac contractility by modulating cAMP levels in various subcellular compartments. These studies have further uncovered contributions of PDE4B and PDE4D in preventing ventricular arrhythmias.
环核苷酸磷酸二酯酶（PDEs）是一大类酶，通过控制其降解速度来调节细胞内两种第二信使 cAMP 和 cGMP 的水平。哺乳动物中存在超过 60 种同工酶，分为 11 个基因家族（PDE1-11），至少有 6 个家族（PDE1-5 和 PDE8）存在于哺乳动物心脏中。与心脏收缩强度调节有关的两种主要家族是 PDE3 和 PDE4。使用转基因模型结合家族特异性 PDE 抑制剂的研究表明，PDE3A、PDE4B 和 PDE4D 同工酶通过调节各种亚细胞隔室内的 cAMP 水平来调节心脏收缩性。这些研究进一步揭示了 PDE4B 和 PDE4D 在预防心室性心律失常中的作用。
