Differential localization of endothelin ET_a and ET_B binding sites in human placenta

Abstract

1 The localization and differential distribution of endothelin (ET) receptor subtypes (ETA and ETB) was investigated in sections of human placenta by use of quantitative in vitro autoradiography and receptor selective ligands.2 Specific, high density ['251]-ET-1 binding sites were localized to the decidua and foetal membranes as well as to arteries and veins in the chorionic plate and throughout the villous tree. Moderate to low density binding was found in the extravillous and villous trophoblast respectively. 6 ET may have a local autocrine or paracrine role in the placenta, acting via specific receptors to influence foetoplacental blood flow and other aspects of placental function.

Endothelin receptor subtypes in the microvillous trophoblastic membrane of early gestation and term human placentas

“…This is compatible with the results obtained in whole placental membranes showing a decrease in the ET-R concentration from the first to the third trimester of pregnancy (13,14). The term placenta appears to be an important source of ETs.…”

“…In term placentas, ET A -R predominates in the proximal regions of vessels in the chorionic plate and stem villi, whereas ET B -R is concentrated on intermediate and terminal villi and on the decidua (14,29). The syncytiotrophoblast, which lines the intervillous space containing maternal blood, can be compared with a fetal endothelial layer.…”

“…The human placenta is a very complex endocrine organ and the ET system in each placental cell seems to develop and change during gestation (12). Specific high affinity ET-1 binding sites have been shown on fetoplacental vessels, trophoblasts and plasma membranes purified from the syncytiotrophoblast of term placentas (13)(14)(15). Transport through the microvillous membrane is the first step in placental transfer.…”

The control of blood flow to the placenta

“…Endothelin is a powerful constrictor of the fetoplacental resistance vasculature (MacLean, Templeton & McGrath, 1992) and raised fetal serum endothelin-1 (ET-1) concentrations have been reported at delivery in pregnancies associated with fetal hypoxia (Ohno, Mizutani, Kurauchi, Nishida, Arii & Tomoda, 1995). ETA and ETB have been identified in the human placental vasculature (Rutherford, Whorton, McCarthy, Gordon, Sullivan, Elder & Polak, 1993), endothelin is present in umbilical vessels (Haegerstrand, Hemsen, Gillis, Larsson & Lundberg, 1989) and ET-1 occurs at higher concentrations in fetal than in maternal blood (Hakkinen, (Maiggard, Forman & Andersson, 1986b) and has no effect in smaller branches of stem villous arteries (McCarthy, Woolfson, Evans, Davis, Raju & Poston, 1994). There is an intact renin-angiotensin system in the placenta.…”

The Expression and Localization of Neutral Endopeptidase 24.11/CD10 in Human Gestational Trophoblastic Diseases

“…For example, GnRH and GnRH receptor were coexpressed in placental trophoblasts and GnRH induced hCG secretion from the trophoblasts via its receptor, indicating the paracrine/ autocrine regulation of hCG secretion by GnRH (Lin et al, 1995;Wolfahrt et al, 1998). ET-1 was produced and localized in the human trophoblasts (Malassine et al, 1993;Marinoni et al, 1995;Myatt et al, 1992) and ET-1 receptors were also present on the membranes of placental trophoblasts (Mondon et al, 1998;Rutherford et al, 1993), suggesting a paracrine or autocrine action of ET-1 in trophoblast function. Because NEP regulates the degradation and processing of bioactive peptides such as GnRH and ET-1 (Erdös and Skidgel, 1989;Flouret et al, 1987;Medeiros et al, 1991;Vijayaraghavan et al, 1990), it is speculated that NEP expressed on the surface of normal syncytiotrophoblast may play a role in the secretion of hCG or other trophoblastic functions by modulating the concentration and receptor binding of these peptides.…”