ENDOTHELIN RECEPTOR SUBTYPES IN THE MICROVILLOUS TROPHOBLASTIC MEMBRANE OF EARLY GESTATION AND TERM HUMAN PLACENTAS

The I-125-labeled endothelin-l ([I-125]ET-1) binding sites in microvil lous membranes from early gestation and term human placentas were inve stigated. The KdS for [I-125]ET-1 binding to early gestation (68 +/- 1 5 pmol/l) and term (45 +/- 8 pmol/l) microvilli (n = 4) were not signi ficantly different. The density of binding sites decreased significant ly, from 243 +/- 80 fmol/mg protein in early gestation microvilli to 5 4 +/- 10 fmol/mg protein in term microvilli. The endothelin (ET) recep tor (ET-R) subtype profiles were determined by competition binding stu dies with unlabeled ET-1, ET-3, and selective agonists and antagonists for ETA-R and ETB-R. In early gestation placental microvilli, we obse rved the presence of 72% ETB-R, (mainly ETB2-R subtype), and 28% ETA-R . Only ETB-R (mainly the ETB2-R subtype) was present in term placental microvilli. We suggest that the ETB-R on the placental microvillous m embrane is involved in specific trophoblastic functions and may play a major role in ET clearance by modulating the amounts of ETs in the ma ternal intervillous blood space.