Endothelin-1 regulates human decidual cells through both A- and B-type receptors

Abstract

The aims of this study were to investigate the effects of endothelin-1 (ET-1) on first trimester human decidual cells, identify the ET receptor sub-types through which these effects are mediated and assess the role of cyclic AMP in any effects of ET-1. ET-1 increased prostaglandin production by first trimester decidual cells, which was consistent with similar studies in third trimester decidual cells. The endothelin A-type receptor (ET A) was coupled to the increased prostaglandin production from first trimester cells, as shown by the inhibitory effects of BQ610, an ET A receptor antagonist. The time course of this effect was unusual, with a rapid increase peaking after 6 h of stimulation, followed by a longer effect over 12–24 h, which was paralleled by changes in cyclic AMP production. No evidence was obtained for any involvement of cyclic AMP in mediating the effects of ET-1 on prostaglandin production. ET-1 also increased decidual prolactin production with a maximum effect after 6 h of stimulation. This was mediated through the ET B receptor and may be linked to increased cyclic AMP production, indicating that the ET A and ET B receptors were coupled to different second messenger systems and affected decidual cell function in different ways.