The endothelin receptor antagonist, BQ-123, inhibits angiotensin II-induced contractions in rabbit aorta.
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.
Webb
M L
ML
Department of Cardiovascular Biochemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, N.J. 08543-4000.
Dickinson
K E
KE
Delaney
C L
CL
Liu
E C
EC
Serafino
R
R
Cohen
R B
RB
Monshizadegan
H
H
Moreland
S
S
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
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