Dey I, Lejeune M, Chadee K
Department of Microbiology and Infectious Disease, Health Sciences Centre, University of Calgary, Calgary, Alberta, Canada.
Br J Pharmacol. 2006 Nov;149(6):611-23. doi: 10.1038/sj.bjp.0706923. Epub 2006 Oct 2.
Prostaglandin E2 (PGE2) is one of the most important biologically active prostanoids found throughout the gastrointestinal tract. Despite the fact that PGE2 regulates many physiological functions of the gut including mucosal protection, gastrointestinal secretion and motility, it is implicated in the pathophysiology of inflammatory bowel diseases (IBD) and colorectal neoplasia. The varied biological functions exerted by PGE2 are through the pharmacologically distinct, G-protein coupled plasma membrane receptors termed EP receptors. Disruptions of various prostanoid receptor genes have helped in unravelling the physiological functions of these receptors. To date, all four subtypes of EP receptors have been individually knocked out in mice and various phenotypes have been reported for each subtype. Similarly, in vitro and in vivo studies using EP receptor agonists and antagonists have helped in uncoupling the diverse functions of PGE2 signalling involving distinct EP receptors in the gut. In this review, we will summarize and conceptualize the salient features of EP receptor subtypes, their regional functions in the gut and how expressions of EP receptors are altered during disease states.
前列腺素E2(PGE2)是在整个胃肠道中发现的最重要的生物活性类前列腺素之一。尽管PGE2调节肠道的许多生理功能,包括粘膜保护、胃肠分泌和运动,但它与炎症性肠病(IBD)和结直肠癌的病理生理学有关。PGE2发挥的多种生物学功能是通过药理学上不同的G蛋白偶联质膜受体(称为EP受体)实现的。各种类前列腺素受体基因的破坏有助于阐明这些受体的生理功能。迄今为止,EP受体的所有四种亚型已在小鼠中分别敲除,并且每种亚型都报道了各种表型。同样,使用EP受体激动剂和拮抗剂的体外和体内研究有助于区分涉及肠道中不同EP受体的PGE2信号传导的多种功能。在这篇综述中,我们将总结并概念化EP受体亚型的显著特征、它们在肠道中的区域功能以及在疾病状态下EP受体的表达如何改变。