Harris T E, Squires P E, Michael A E, Bernal A L, Abayasekara D R
Reproduction and Development Group, Department of Veterinary Basic Sciences, Royal Veterinary College, London, NW1 0TU, United Kingdom.
Biochem Biophys Res Commun. 2001 Aug 3;285(5):1089-94. doi: 10.1006/bbrc.2001.5301.
Prostaglandin E(2) (PGE(2)) exerts mainly luteotrophic effects in the corpus luteum. In other tissues, PGE(2) acts via specific PGE(2) receptor subtypes including EP1, which modulates intracellular calcium (Ca(2+)) and EP2, which is coupled to cyclic AMP (cAMP) generation. We have therefore investigated the presence of functional EP1 and EP2 receptors using human granulosa-lutein (GL) cells. Reverse-transcription PCR revealed that GL cells expressed mRNA transcripts encoding both EP1 and EP2 receptors. When GL cells were challenged with ligands that can bind to both receptor subtypes (PGE(2) and 16,16 dimethyl PGE(2)) or exclusively to EP2 (butaprost), both cAMP formation and progesterone synthesis were stimulated. Furthermore, the cAMP response to these agonists could be significantly blocked by an EP1/2 antagonist AH6809 but not by an EP1-selective antagonist SC19220. Exposure of GL cells to 16,16-dm PGE(2) transiently raised Ca(2+) levels, which could be prevented by both AH6809 and SC19220. We therefore conclude that human GL cells express functional EP1 and EP2 receptors.
前列腺素E(2)（PGE(2)）在黄体中主要发挥黄体营养作用。在其他组织中，PGE(2)通过特定的PGE(2)受体亚型发挥作用，包括调节细胞内钙（Ca(2+)）的EP1和与环磷酸腺苷（cAMP）生成偶联的EP2。因此，我们使用人颗粒黄体（GL）细胞研究了功能性EP1和EP2受体的存在情况。逆转录聚合酶链反应显示，GL细胞表达编码EP1和EP2受体的mRNA转录本。当用可与两种受体亚型结合的配体（PGE(2)和16,16-二甲基PGE(2)）或仅与EP2结合的配体（布他前列素）刺激GL细胞时，cAMP生成和孕酮合成均受到刺激。此外，这些激动剂引起的cAMP反应可被EP1/2拮抗剂AH6809显著阻断，但不能被EP1选择性拮抗剂SC19220阻断。将GL细胞暴露于16,16-二甲基PGE(2)可使Ca(2+)水平短暂升高，AH6809和SC19220均可阻止这种升高。因此，我们得出结论，人GL细胞表达功能性EP1和EP2受体。
