Petit A, Guillon G, Tence M, Jard S, Gallo-Payet N, Bellabarba D, Lehoux J G, Belisle S
Faculty of Medicine, University of Sherbrooke, Quebec, Canada.
J Clin Endocrinol Metab. 1989 Aug;69(2):280-6. doi: 10.1210/jcem-69-2-280.
We studied the functional significance of the binding of angiotensin-II (AII) to human placentas. Human trophoblastic cell suspensions were prepared by trypsin digestion of minced tissue. Cell incubations with increasing doses of 125IAII, ranging from 0.01-2.5 nmol/L, were carried out for 20 min at 37 C. The results indicated the presence of specific low capacity [4300 +/- 1300 (+/- SE) sites/cell], high affinity (Kd = 0.38 +/- 0.06 nmol/L) binding sites for 125IAII. This binding was specific for AII analogs. When placental cells were preloaded with 40 microCi/mL [3H]myoinositol for 2 h at 37 C, AII stimulation resulted in a dose-dependent increase in inositol phosphate (InsP) production [EC50 = 1.4 +/- 0.4 (+/- SE) nmol/L], as measured by ion exchange chromatography. (Sar1)AII also stimulated InsP production, with an EC50 of 0.3 +/- 0.2 nmol/L. AII-stimulated production of InsP was completely blocked by the antagonist (Sar1,Ala8)AII. AII also stimulated human placental lactogen release from trophoblastic cells in a dose-dependent fashion. The EC50 was 18 +/- 9 pmol/L, and the stimulation was blocked by (Sar1,Ala8)AII, as found for AII-stimulated InsP production. These results suggest that stimulation of human placental lactogen release by AII may be mediated by activation of phospholipase-C, which, in turn, produces phosphoinositide breakdown. The results, therefore, provide evidence of a physiological role for the renin-angiotensin system within the human placenta.
我们研究了血管紧张素-II（AII）与人胎盘结合的功能意义。通过胰蛋白酶消化切碎的组织制备人滋养层细胞悬液。在37℃下用0.01 - 2.5 nmol/L递增剂量的125IAII进行细胞孵育20分钟。结果表明存在特异性低容量[4300±1300（±标准误）个位点/细胞]、高亲和力（解离常数Kd = 0.38±0.06 nmol/L）的125IAII结合位点。这种结合对AII类似物具有特异性。当胎盘细胞在37℃下用40微居里/毫升[3H]肌醇预加载2小时后，通过离子交换色谱法测定，AII刺激导致肌醇磷酸（InsP）生成呈剂量依赖性增加[半数有效浓度EC50 = 1.4±0.4（±标准误）nmol/L]。(Sar1)AII也刺激InsP生成，EC50为0.3±0.2 nmol/L。AII刺激的InsP生成被拮抗剂(Sar1,Ala8)AII完全阻断。AII还以剂量依赖性方式刺激滋养层细胞释放人胎盘催乳素。EC50为18±9皮摩尔/升，并且如AII刺激的InsP生成情况一样，这种刺激被(Sar1,Ala8)AII阻断。这些结果表明，AII刺激人胎盘催乳素释放可能是通过磷脂酶-C的激活介导的，而磷脂酶-C进而导致磷酸肌醇分解。因此，这些结果为肾素-血管紧张素系统在人胎盘中的生理作用提供了证据。
