Terry K K, Lebel W S, Riccardi K A, Grasser W A, Thompson D D, Paralkar V M
Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA.
Prostaglandins Leukot Essent Fatty Acids. 2008 Jan;78(1):3-10. doi: 10.1016/j.plefa.2007.10.003. Epub 2007 Nov 26.
Prostaglandin E(2) (PGE(2)) exerts diverse biological effects through four G-protein-coupled cell surface receptor subtypes, EP1-4. This study's objective was to characterize EP1-4 receptor mRNA expression within pregnant guinea pig myometrium during early implantation stage (gestation day [GD] 6) and late stage gestation (GD 50) and evaluate in vitro contractile activity of receptor subtype selective agonists. Using RT-PCR, qualitative gene expression patterns of EP2, EP3, and EP4 mRNA were detected in the myometrium and remained unchanged between the gestational ages. EP1 mRNA remained undetected in pregnant tissue. In vitro contractile activity was evaluated in GD 6 and GD 50 myometrium using vehicle and EP agonists PGE(2), 17-phenyl trinor PGE(2), sulprostone, misoprostol, and CP-533,536. All spasmogens in pregnant myometrium were EP1/EP3 selective agonists, though likely acting via EP3 receptors in this test model. CP-533,536--a highly selective EP2 receptor agonist--and the vehicle failed to induce myometrial contraction at both gestational ages.
前列腺素E(2)（PGE(2)）通过四种G蛋白偶联细胞表面受体亚型EP1 - 4发挥多种生物学效应。本研究的目的是表征妊娠豚鼠子宫肌层在植入早期（妊娠第[GD]6天）和妊娠晚期（GD 50）时EP1 - 4受体mRNA的表达，并评估受体亚型选择性激动剂的体外收缩活性。使用逆转录聚合酶链反应（RT-PCR），在子宫肌层中检测到EP2、EP3和EP4 mRNA的定性基因表达模式，且在不同胎龄之间保持不变。在妊娠组织中未检测到EP1 mRNA。使用赋形剂和EP激动剂PGE(2)、17-苯基三降PGE(2)、硫前列酮、米索前列醇和CP-533,536评估GD 6和GD 50子宫肌层的体外收缩活性。妊娠子宫肌层中的所有致痉剂均为EP1/EP3选择性激动剂，不过在该测试模型中可能是通过EP3受体起作用。CP-533,536（一种高度选择性的EP2受体激动剂）和赋形剂在两个胎龄均未诱导子宫肌层收缩。
