In vitro characterisation of Ro 46-8443, the first non-peptide antagonist selective for the endothelin ETB receptor.
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.
Breu
V
V
Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Clozel
M
M
Burri
K
K
Hirth
G
G
Neidhart
W
W
Ramuz
H
H
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001667:Binding, Competitive; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D065128:Endothelin Receptor Antagonists; D006801:Humans; D066298:In Vitro Techniques; D008861:Microsomes / Q000378:metabolism; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D011485:Protein Binding; D011743:Pyrimidines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000378:metabolism; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013449:Sulfonamides / Q000378:metabolism / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000378:metabolism; D014757:Viper Venoms / Q000378:metabolism; D000096926:Benzenesulfonamides
D016718:Arachidonic Acid; D065128:Endothelin Receptor Antagonists; D011743:Pyrimidines; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D018000:Receptors, Peptide; D011994:Recombinant Proteins; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C099180:Ro 46-8443; D000096926:Benzenesulfonamides; C058085:sarafotoxin receptor; C057354:sarafotoxins s6