Angiotensin II Stimulates Both Inositol Phosphate Production and Human Placental Lactogen Release from Human Trophoblastic Cells

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Abstract
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 [125I] (Sar1)AII, 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 [125I](Sar1)AII. This binding was specific for AII analogs. When placental cells were preloaded with 40 .mu.Ci/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.