title: ETA receptors are present in human aortic vascular endothelial cells and modulate intracellular calcium.
abstract: Using immunofluorescence and real 3-D confocal microscopy, our results showed the presence of ET-1, ETA, and ETB receptors in isolated human aortic vascular endothelial cells (hVECs). The level of the peptide and its receptors was significantly higher in the nucleus (including the nuclear envelope membranes) than in the cytosol (including the cell membrane). Furthermore, using the Western blot technique we demonstrated the presence of both ETA and ETB receptors. Using intact and isolated human hVECs and the Fura-2 calcium (Ca2+) measurement technique, we showed that ET-1 induced a dose-dependent increase of total intracellular free Ca2+, with an EC50 of 1.3 x 10-10 mol/L. The specific ETA receptor antagonist ABT-627 (10-7 mol/L), but not the ETB receptor antagonist A-192621 (10-7 mol/L), prevented the ET-1 (10-9 mol/L) induced increase of total intracellular Ca2+. In conclusion, these results clearly show that similar to ETB receptors, ETA receptors are also present in human aortic vascular endothelial cells and their levels are higher than ETB in the nucleus when compared with the cytosol. Furthermore, we suggest that ETA, but not ETB, receptors mediate the effect of ET-1 on total intracellular Ca2+ of human aortic vascular endothelial cells.
authors: Department of Anatomy and Cell Biology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, QC J1H5N4, Canada.
authors: Levon
authors: L
authors: Avedanian
authors: Julie
authors: J
authors: Riopel
authors: Ghassan
authors: G
authors: Bkaily
authors: Moni
authors: M
authors: Nader
authors: Pedro
authors: P
authors: D'Orleans-Juste
authors: Danielle
authors: D
authors: Jacques
mesh_terms: D000293:Adolescent; D000328:Adult; D001011:Aorta / Q000166:cytology*; D000077868:Atrasentan; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology; D006801:Humans; D008875:Middle Aged; D011759:Pyrrolidines / Q000494:pharmacology; D044022:Receptor, Endothelin A / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000378:metabolism; D055815:Young Adult
chemical_list: C120508:A 192621; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D011759:Pyrrolidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D004533:Egtazic Acid; D000077868:Atrasentan