Self-regulation of the endothelin receptor system in choriocarcinoma cells

The human trophoblast secretes endothelin-l (ET-1) and expresses ET recepto rs. The present study tested whether the transformed BeWo, JAR and JEG-3 ch oriocarcinoma cells: (1) secrete endothelin-l (ET-I); (2) express both ET-A and ET-B receptor subtypes; and (3) have the potential to allow for autolo gous regulation of ET-receptor proteins. The cells were cultured for 24/48 h with or without 10% FCS and, in experiments on receptor regulation, with ET-I (5-20 nM and 10 CIM). ET-I secretion was measured by RIA and receptor levels by immunoblotting. All cell types secreted ET-1 albeit at different levels and sensitivity to FCS. All cell lines expressed both ET-A (JEC-3 > BeWo = JAR) and ET-B (JEG-3 = JAR > BeWo) receptor subtypes, which could be up- and downregulated depending on ET-I concentration, culture time and FC S presence. It is concluded that BeWo, JAR and JEG-3 choriocarcinoma cells secrete ET-1 and express both ET-A and ET-B receptor subtypes. The receptor levels can be regulated by ET-I. This provides the molecular basis for an autocrine system with the potential of autologous regulation of yet unident ified ET-l-induced functions. (C) 2000 Elsevier Science B.V. All rights res erved.