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- W1969264369 abstract "Our previous report suggests the important role that ETB receptors play in the clearance of circulating endothelin (ET)-1. The present study confirmed this finding by measuring the extracellular levels of immunoreactive (ir) ET-1 and intracellular contents of prepro (pp) ET-1 mRNA in the presence and absence of ETA- and ETB-selective antagonists (i.e., BQ-123 and BQ-788, respectively) in cultured human umbilical vein endothelial cells (HUVECs). ET-1 was secreted into the culture medium of HUVECs in a time-dependent manner with a plateau reached after incubation for more than 36 hr. In the presence of 10 microM BQ-788, the irET-1 level was enhanced significantly (i.e., up to 180% of control at 48 hr) whereas BQ-123 had no such effect. Specific binding of [125I]ET-1 to HUVECs was inhibited strongly by BQ-788 (IC50 = 2.4 nM) but very weakly by BQ-123 (IC50 = 1.4 microM), indicating that BQ-788 has a potent affinity for ETB receptors in HUVECs. The expression of ppET-1 mRNA was not changed by BQ-788. Extracellular levels of ET-1 decreased gradually after cellular treatment with cycloheximide. This decrease was significantly inhibited by BQ-788 but not by BQ-123 and was non-existent when the cells were incubated at 4 degrees C (where internalization of the receptor protein is not likely). In conclusion, HUVECs secrete ET-1 which, in turn, is internalized after binding to ETB receptors on HUVECs." @default.
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- W1969264369 date "1995-04-01" @default.
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- W1969264369 title "ETB-Mediated Regulation of Extracellular Levels of Endothelin-1 in Cultured Human Endothelial Cells" @default.
- W1969264369 doi "https://doi.org/10.1006/bbrc.1995.1527" @default.
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