Nemoto K, Pilbeam C C, Bilak S R, Raisz L G
Department of Medicine, University of Connecticut Health Center, Farmington 06030, USA.
Prostaglandins. 1997 Oct;54(4):713-25. doi: 10.1016/s0090-6980(97)00145-7.
Prostaglandin E2 (PGE2) is a potent local mediator of cell growth and differentiation in various tissues. The receptors for PGE2 have been classified into four pharmacological subtypes, EP1, EP2, EP3, and EP4, based on the responses to selective agonists and antagonists. We have cloned a functional cDNA for the rat EP2 receptor subtype from a rat lung cDNA library. The rat EP2 receptor cDNA encodes 357 amino acid residues having high homology with the human and mouse EP2 receptors and containing seven putative transmembrane domains. In COS-7 cells transfected with rat EP2 cDNA, specific [3H]PGE2 binding was found with a dissociation constant of 14.9 nM, and this binding was inhibited by unlabeled PGE2 and PGE2 alpha. PGE2 and butaprost, an EP2 selective agonist, were effective in increasing the cAMP level in the COS-7 cell transfectants. Northern blot and RT-PCR analysis showed widespread distribution of the EP2 receptor in various tissues. Higher EP2 expression was found in fetal long bones and calvariae than in adult by RT-PCR and in situ hybridization, suggesting a role for this receptor in rapidly growing skeletal tissue.
前列腺素E2（PGE2）是多种组织中细胞生长和分化的强效局部介质。基于对选择性激动剂和拮抗剂的反应，PGE2的受体已被分为四种药理学亚型，即EP1、EP2、EP3和EP4。我们从大鼠肺cDNA文库中克隆了大鼠EP2受体亚型的功能性cDNA。大鼠EP2受体cDNA编码357个氨基酸残基，与人及小鼠的EP2受体具有高度同源性，并含有七个假定的跨膜结构域。在用大鼠EP2 cDNA转染的COS-7细胞中，发现特异性的[3H]PGE2结合，解离常数为14.9 nM，且这种结合被未标记的PGE2和PGE2α抑制。PGE2和EP2选择性激动剂布他前列素可有效提高COS-7细胞转染子中的cAMP水平。Northern印迹和RT-PCR分析显示EP2受体在各种组织中广泛分布。通过RT-PCR和原位杂交发现，胎儿长骨和颅骨中的EP2表达高于成人，提示该受体在快速生长的骨骼组织中发挥作用。
