Two subtypes of endothelin receptors and endothelin peptides are expressed in differential cell types of the rat placenta: in vitro receptor autoradiographic and in situ hybridization studies.

We studied the localization of endothelin (ET) receptors and ET peptides in the rat placenta. In vitro receptor autoradiographic and in situ hybridization studies revealed the differential and cell-specific distribution of ET receptor subtypes, suggesting that each ET receptor plays a different role in the function of the placenta. The expression of the ETB receptor was concentrated to cytotrophoblasts and trophoblastic giant cells of the basal zone, in which fetal cells directly face maternal cells. The ETA receptor was confined to the decidual tissue and vascular wall. Both ET receptors coexisted in the labyrinth in an approximately 50:50 ratio. Prepro-ET-1 messenger RNA (mRNA) was detected in cytotrophoblasts and trophoblastic giant cells of the basal zone and endothelial cells of vessels, whereas ET-1-like immunoreactivity was present not only in trophoblasts and endothelial cells, but also in the decidual tissue and vascular wall. ET-3 mRNA was localized in migrating cells. We also found changes in the expression levels of ET receptors by means of a cold ligand saturation study. The number of specific [125I]ET-1-binding sites was increased in the basal zone and labyrinth with gestation, but not in the decidual tissue. The enhancement of ETA receptor, ETB receptor, and prepro-ET-1 mRNA levels was also supposed, based on data obtained by RT-PCR Southern hybridization. On the other hand, ET-3 mRNA levels were reduced with gestation. These findings support the idea that ETs, through interaction with ETA and ETB receptors, play an important role in the regulation of placental growth and fetoplacental circulation through autocrine and paracrine mechanisms.