Two types of endothelin B receptors mediating relaxation in the guinea pig ileum.
In guinea pig ileum, binding assays showed the existence of endothelin (ET) receptors of ETA (isopeptide-selective) and ETB (nonselective) subtypes. ETs induced relaxation followed by contraction. ET-1 induced greater contraction at lower concentrations than ET-3. An ETA antagonist, BQ-123, shifted the concentration-response curves for ETs to the right. An ETB antagonist, IRL 1038, shifted the concentration-response curve for ET-3 to the right and downwards with little effect on the curve for ET-1. In contrast, ET-1 and ET-3 induced relaxation at similar concentrations. The relaxation induced by ETs was composed of an initial transient relaxation followed by sustained relaxation. Only the transient phase was inhibited by IRL 1038 in a concentration-dependent manner. These results suggest that the ET-induced relaxation is mediated by two types of ETB receptor; transient and sustained relaxations are mediated respectively by IRL 1038-sensitive and IRL 1038-insensitive subtypes of ETB receptor. In contrast, the contractile effect seems to be mediated mainly by the ETA receptor and partially by an IRL 1038-sensitive subtype of ETB receptor.
Hori
M
M
Department of Veterinary Pharmacology, Faculty of Agriculture, University of Tokyo, Japan.
Sudjarwo
S A
SA
Oda
K
K
Urade
Y
Y
Karaki
H
H
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000187:drug effects / Q000378:metabolism*
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; C074308:sovateltide; C077420:Cys(11)-Cys(15)-endothelin-1 (11-21); C072247:cyclo(Trp-Asp-Pro-Val-Leu)