Endothelin-1 induces rapid and long lasting internalization of the thrombin receptor in human glomerular epithelial cells.
Endothelin-1 acts as a potent autocrine and paracrine mediator in the kidney. Glomeruli and renal arterioles also express functional thrombin receptors which mediate the cellular effects of thrombin. Using the binding on glomerular epithelial cells of 125I-labeled ATAP2, a monoclonal antibody raised against the functional thrombin receptor, we demonstrate here that endothelin-1 induces thrombin receptor internalization in a dose- and a time-dependent manner. The maximal effect is observed at 10(-7) M endothelin-1 corresponding to internalization of approximately 25% of thrombin receptors. It is maximal at 20 min and persists for at least 24 h. This effect is mediated by the endothelin receptor subtype A (ETA), and involves a pertussis toxin-sensitive G-protein and protein kinase C activation. Endothelin-1 does not induce thrombin receptor degradation nor change in thrombin receptor mRNA level after 2 h and 24 h of incubation. These results indicate that partial heterologous internalization of the functional thrombin receptor is induced by endothelin-1.
Chen
X
X
INSERM, Unité 64, Hôpital Tenon, Paris, France.
Berrou
J
J
Nguyen
G
G
Sraer
J D
JD
Rondeau
E
E
D002478:Cells, Cultured; D015536:Down-Regulation; D004705:Endocytosis; D016232:Endothelins / Q000502:physiology*; D004789:Enzyme Activation; D004848:Epithelium / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism*; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000378:metabolism; D018179:Receptors, Thrombin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D016232:Endothelins; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D018179:Receptors, Thrombin; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D011493:Protein Kinase C; D019204:GTP-Binding Proteins