Abstract
The effects of a novel cyclic pentapeptide (BQ-123), an endothelin (ET) antagonist selective for the ETA receptor subtype, on phosphoinositide breakdown and DNA synthesis stimulated by ET-1 were studied in cultured rat vascular smooth muscle cells (VSMC). BQ-123 competitively inhibited the binding of [125I]ET-1 to VSMC with the apparent Ki of 4 x 10(-9) M. BQ-123 dose-dependently inhibited formation of inositol-1,4,5-trisphosphate and [3H]thymidine uptake stimulated by ET-1. These data suggest that the ET-1-induced DNA synthesis in VSMC is mainly mediated by ETA receptor subtype.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding, Competitive
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Cells, Cultured
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DNA / biosynthesis*
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Endothelins / antagonists & inhibitors
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Endothelins / metabolism
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Endothelins / pharmacology*
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Male
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / metabolism*
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Peptides, Cyclic / pharmacology*
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Phosphatidylinositols / metabolism*
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Rats
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Rats, Inbred Strains
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Receptors, Cell Surface / antagonists & inhibitors*
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Receptors, Endothelin
Substances
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Endothelins
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Peptides, Cyclic
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Phosphatidylinositols
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Receptors, Cell Surface
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Receptors, Endothelin
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DNA
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cyclo(Trp-Asp-Pro-Val-Leu)