Angiotensin II stimulates both inositol phosphate production and human placental lactogen release from human trophoblastic cells.
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 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.
Petit
A
A
Faculty of Medicine, University of Sherbrooke, Quebec, Canada.
Guillon
G
G
Tence
M
M
Jard
S
S
Gallo-Payet
N
N
Bellabarba
D
D
Lehoux
J G
JG
Belisle
S
S
D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology*; D001665:Binding Sites; D001667:Binding, Competitive; D002852:Chromatography, Ion Exchange; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis*; D010716:Phosphatidylinositols / Q000378:metabolism; D010928:Placental Lactogen / Q000378:metabolism*; D011247:Pregnancy; D013403:Sugar Phosphates / Q000096:biosynthesis*; D013696:Temperature; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*; D014357:Trypsin
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D013403:Sugar Phosphates; D000804:Angiotensin II; D010928:Placental Lactogen; D014357:Trypsin