Synthesis and release of endothelin-1 by human decidual cells.
We have studied whether a novel vasoconstrictor, endothelin-1 (ET-1), is synthesized by and released from human decidual cells in early pregnancy, and whether ET-1 acts directly on their own cells. It was observed that ET-1-like immunoreactivity (ET-1-LI) was released from cultured decidual, but not villous, cells, as a function of time. Reverse-phase high-pressure liquid chromatography of the conditioned media from the decidual cells revealed a major peak of ET-1-LI coeluting with standard ET-1. Phorbol myristate acetate, a protein kinase C activator, dose-dependently increased the release of ET-1-LI from the decidual cells, while a protein kinase C inhibitor, H7, significantly attenuated the stimulatory effect of phorbol myristate acetate on ET-1-LI release. Northern blot analysis demonstrated the expression of messenger RNA for prepro-ET-1 in the decidual tissue, but no such messenger RNA was observed in the villous tissue. The human decidual tissue contained a noninteracting, single class of binding sites demonstrating higher affinity for ET-1 and ET-2 than ET-3. This would be most consistent with the ETA receptor subtype. An ET-1-induced, dose-dependent accumulation of total inositol phosphates was also observed in human decidual cells prelabeled with myo-[3H]inositol. The present results demonstrate for the first time that human decidual cells in early pregnancy can synthesize and release ET-1. These cells also possess specific functional receptors for ET-1 which are coupled to phosphoinositide hydrolysis. Thus our data suggest a possible role for ET-1 in autocrine and/or paracrine function in human decidual cells.
Kubota
T
T
Department of Obstetrics and Gynecology, Tokyo Medical and Dental University, Faculty of Medicine, Japan.
Kamada
S
S
Hirata
Y
Y
Eguchi
S
S
Imai
T
T
Marumo
F
F
Aso
T
T
D001667:Binding, Competitive; D015152:Blotting, Northern; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media; D003656:Decidua / Q000166:cytology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011863:Radioimmunoassay
D003470:Culture Media; D016232:Endothelins; D007295:Inositol Phosphates; D012333:RNA, Messenger