Kobayashi Takuya, Narumiya Shuh
Department of Pharmacology, Faculty of Medicine, Kyoto University, Japan.
Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:557-73. doi: 10.1016/s0090-6980(02)00055-2.
Prostanoids consisting of the prostaglandins (PGs) and the thromboxanes (TXs) are the cyclooxygenase metabolites of arachidonic acid. They exert a range of actions mediated by their respective receptors expressed in the target cells. The receptors include the DP, EP, FP, IP and TP receptors for PGD, PGE, PGF, PGI and TXA, respectively. Furthermore, EP is subdivided into four subtypes, EP1, EP2, EP3 and EP4, which are encoded by different genes and differ in their responses to various agonists and antagonists. Recent developments in the molecular biology of the prostanoid receptors have enabled the investigation of physiological roles of each receptor by disruption of the respective gene. At this point, all the eight types and subtypes of the prostanoid receptors have been individually knocked out in mice, and various phenotypes have been reported for each strain. Here, we review the findings obtained in these studies. The results from these knockout mice studies may be useful in the development of novel therapeutics that can selectively manipulate actions mediated by each receptor.
前列腺素(PGs)和血栓素(TXs)组成的类前列腺素是花生四烯酸的环氧化酶代谢产物。它们通过在靶细胞中表达的各自受体介导一系列作用。这些受体分别包括DP、EP、FP、IP和TP受体,分别对应PGD、PGE、PGF、PGI和TXA。此外,EP分为四种亚型,即EP1、EP2、EP3和EP4,它们由不同基因编码,对各种激动剂和拮抗剂的反应也不同。类前列腺素受体分子生物学的最新进展使得通过破坏各自基因来研究每个受体的生理作用成为可能。此时,类前列腺素受体的所有八种类型和亚型已在小鼠中分别敲除,并且已报道了每个品系的各种表型。在此,我们综述这些研究中获得的发现。这些基因敲除小鼠研究的结果可能有助于开发能够选择性操纵由每个受体介导的作用的新型疗法。