磷酸二酯酶及其抑制剂的研究进展

Research progress of phosphodiesterases and phosphodiesterase inhibitors

磷酸二酯酶(PDEs)是一类可水解细胞内第二信使环磷酸腺苷(cyclic adenosine monophosphate,cAMP)和环磷酸鸟苷(cyclic guanosine monophosphate,cGMP)的酶类,可调节细胞内的多种信号传递和生理活动。PDEs由11种不同的家族组成,且各家族包含不同的亚型,各个亚型在细胞内分布、表达、调节方式以及对抑制剂的敏感性均不同,参与了炎症、哮喘、抑郁、勃起功能障碍等多种病理过程的发生发展,这些特点使得PDE作为新的药物靶点得到了越来越多的关注。该文将从PDE各家族生物学特点、生理病理学意义及其抑制剂的应用作一简单综述。

Intracellular levels of ubiquitous transduction signal cyclic adenosine 3＇, 5＇-monophosphate （cAMP） and cyclic guanosine 3＇, 5＇-monophosphate （cGMP） are partly determined by the hydrolysis by phosphodiesterases （PDEs）. So far, the su-perfamily of PDE is composed of at least 11 isoforms and each family is characterized with unique cellular distribution, expres- sion, regulation mode and inhibitor sensitivity, and PDEs are considered to be involved in a variety of pathological processes,such as inflammation, asthma, depression, and erectile dysfunc-tion, etc. Currently, these characteristics draw PDEs more and more attention as great targets for drugs. In this review, the bas-ic biochemical properties, cellular regulation, expression pat-tern, physiological functions and inhibitors of different PDE iso- forms will be briefly discussed.