Endothelin-1 stimulates its own synthesis in human endothelial cells.
We studied whether endothelin-1 (ET-1) would affect its own synthesis. Human umbilical cord vein endothelial cells in methionine-poor culture medium containing [35S] methionine were treated with synthetic ET-1 or ET-3. Immunoprecipitation of 35 S-labeled ET-1 was performed with rabbit ET-1 antiserum. ET-1 caused an 40 +/- 4% (mean +/- SEM) increase of immunoprecipitable 35 S-labeled ET-1 as confirmed by its elution point in reversed phase high power liquid chromatography (HPLC). ET-3 caused a 23 +/- 2% increase in ET-1 concentration. Amplification of cDNA by PCR showed both ET-1 and ETB receptor mRNAs in human cord vein endothelial cells. We conclude that ET-1 increases its own synthesis in endothelial cells. This suggests a positive autocrine feed-back action of ET-1 on its own synthesis, an effect which is probably mediated by non-specific ETB receptors.
Saijonmaa
O
O
Minerva Institute for Medical Research, Helsinki, Finland.
Nyman
T
T
Fyhrquist
F
F
D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D016232:Endothelins / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D005246:Feedback; D006801:Humans; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D017466:Receptors, Endothelin / Q000096:biosynthesis / Q000235:genetics; D013462:Sulfur Radioisotopes; D014471:Umbilical Veins
D016232:Endothelins; D012333:RNA, Messenger; D017466:Receptors, Endothelin; D013462:Sulfur Radioisotopes; D008715:Methionine