title: The endothelin receptor antagonist, BQ-123, inhibits angiotensin II-induced contractions in rabbit aorta.
abstract: The purpose of this study was to examine the specificity of the cyclic pentapeptide ET(A) receptor antagonist BQ-123. BQ-123 competitively antagonized endothelin-1-induced contractions in rabbit aorta, increases in inositol phosphates in cultured rat vascular smooth muscle A10 cells, and binding of [125I]endothelin-1 to the cloned ETA receptor cDNA expressed in Cos 7 cells. In contrast, BQ-123 was a weak antagonist of [125I]endothelin-3 binding to rat cerebellar membranes and to membranes from Cos 7 cells transfected with the cloned ETB receptor cDNA. BQ-123 shifted concentration-response curves in isolated rabbit aorta elicited by angiotensin II, but did not bind to angiotensin II receptors nor affect angiotensin II-induced increases in inositol phosphates. BQ-123 also did not affect contractions induced by KCl or norepinephrine. These data suggest that endothelin may play a role in angiotensin II-induced contractions of rabbit aorta.
authors.affiliation: Department of Cardiovascular Biochemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, N.J. 08543-4000.
authors.forename: M L
authors.initials: ML
authors.lastname: Webb
authors.forename: K E
authors.initials: KE
authors.lastname: Dickinson
authors.forename: C L
authors.initials: CL
authors.lastname: Delaney
authors.forename: E C
authors.initials: EC
authors.lastname: Liu
authors.forename: R
authors.initials: R
authors.lastname: Serafino
authors.forename: R B
authors.initials: RB
authors.lastname: Cohen
authors.forename: H
authors.initials: H
authors.lastname: Monshizadegan
authors.forename: S
authors.initials: S
authors.lastname: Moreland
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000378:metabolism*; D003001:Cloning, Molecular; D016232:Endothelins / Q000494:pharmacology* / Q000502:physiology; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D017466:Receptors, Endothelin; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D014162:Transfection
chemical_list: D016232:Endothelins; D007295:Inositol Phosphates; D010456:Peptides, Cyclic; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D011994:Recombinant Proteins; D000804:Angiotensin II; D011189:Potassium Chloride; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D009638:Norepinephrine