Department of Physiology and Functional Genomics, University of Florida College of Medicine, and D. H. Barron Reproductive and Perinatal Biology Research Program, Gainesville, Florida.
Instituto de Investigaciones en Ciencias de la Salud, Consejo Nacional de Investigaciones Científicas y Técnicas, Pabellón de Biología Celular, Córdoba , Argentina.
Am J Physiol Regul Integr Comp Physiol. 2019 May 1;316(5):R628-R639. doi: 10.1152/ajpregu.00153.2018. Epub 2019 Mar 20.
We investigated expression of cholecystokinin (CCK) in humans and mice, and the bitter taste receptor TAS2R14 in the human placenta. Because CCK and gastrin activate the CCKBR receptor, we also explored placental gastrin expression. Finally, we investigated calcium signaling by CCK and TAS2R14. By RT-PCR, we found and mRNA expression in both normal human and mouse placentas, as well as in human trophoblast cell lines (TCL). Although both and - mRNA were expressed in the mouse placenta, only mRNA was detected in the human placenta and TCL. mRNA expression for was also observed in the human placenta and TCL. Using immunohistochemistry, CCK protein was localized to the syncytiotrophoblast (ST) and extravillous trophoblast (EVT) in the human term placenta, and to trophoblast glycogen cells in mouse and human placentas. Gastrin and TAS2R14 proteins were also observed in ST and EVT of the human placenta. Both sulfated and nonsulfated CCK elicited a comparable rise in intracellular calcium in TCL, consistent with expression. Three TAS2R14 agonists, flufenamic acid, chlorhexidine, and diphenhydramine, also evoked rises in intracellular calcium in TCL. These results establish CCK, gastrin, and their receptor(s) in both human and mouse placentas, and TAS2R14 in the human placenta. Both CCK and TAS2R14 agonists increased intracellular calcium in human TCL. Although the roles of these ligands and receptors, and their potential cross talk in normal and pathological placentas, are currently unknown, this study opens new avenues for placental research.
我们研究了胆囊收缩素（CCK）在人类和小鼠中的表达，以及人胎盘上的苦味受体 TAS2R14。由于 CCK 和胃泌素激活 CCKBR 受体，我们还探索了胎盘胃泌素的表达。最后，我们研究了 CCK 和 TAS2R14 的钙信号转导。通过 RT-PCR，我们在正常人和小鼠胎盘以及人滋养层细胞系（TCL）中发现了 CCK 和 gastrin 的 mRNA 表达。虽然人和小鼠胎盘以及 TCL 中均表达了 和 mRNA，但仅在人胎盘和 TCL 中检测到 mRNA。人胎盘和 TCL 中也观察到了 mRNA 的表达。通过免疫组织化学，CCK 蛋白定位于人足月胎盘中的合体滋养层（ST）和细胞滋养层外胚层（EVT），以及小鼠和人胎盘中的滋养层糖原细胞。胃泌素和 TAS2R14 蛋白也在人胎盘的 ST 和 EVT 中观察到。在 TCL 中，硫酸化和非硫酸化的 CCK 均可引起细胞内钙的相似增加，与 表达一致。三种 TAS2R14 激动剂，氟芬那酸、洗必泰、和苯海拉明，也可引起 TCL 内细胞内钙的增加。这些结果在人和小鼠胎盘中建立了 CCK、胃泌素及其受体，以及人胎盘上的 TAS2R14。CCK 和 TAS2R14 激动剂均可增加人 TCL 中的细胞内钙。尽管这些配体和受体的作用，以及它们在正常和病理胎盘中的潜在串扰目前尚不清楚，但本研究为胎盘研究开辟了新的途径。
