Abstract
We describe here Ro 46-8443, the first non-peptide endothelin ETB receptor selective antagonist. It displays up to 2000-fold selectivity for ETB receptors both in terms of binding inhibitory potency and functional inhibition. The observed parallel rightward shift of concentration-response curves with different antagonist concentrations is consistent with a competitive binding mode. Since R0 46-8443 selectively inhibits ETB receptor mediated responses, it is a valuable tool for clarifying the role of ETB receptors in pathology.
MeSH terms
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Animals
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Arachidonic Acid / metabolism
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Binding, Competitive
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CHO Cells
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Cell Membrane / metabolism
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Cricetinae
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Endothelin Receptor Antagonists*
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Humans
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In Vitro Techniques
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Microsomes / metabolism
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Molecular Structure
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Muscle Contraction / drug effects
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Protein Binding
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Pyrimidines / metabolism
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Pyrimidines / pharmacology*
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Rats
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Receptor, Endothelin B
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Receptors, Endothelin / metabolism
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Receptors, Peptide / antagonists & inhibitors
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Receptors, Peptide / metabolism
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Recombinant Proteins / metabolism
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Sulfonamides / metabolism
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Sulfonamides / pharmacology*
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Vasoconstriction / drug effects
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Vasoconstrictor Agents / metabolism
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Viper Venoms / metabolism
Substances
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Endothelin Receptor Antagonists
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Pyrimidines
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Receptor, Endothelin B
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Receptors, Endothelin
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Receptors, Peptide
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Recombinant Proteins
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Ro 46-8443
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Sulfonamides
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Vasoconstrictor Agents
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Viper Venoms
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sarafotoxin receptor
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sarafotoxins s6
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Arachidonic Acid