Heterogeneous endothelin receptors mediate relaxation and contraction in the guinea-pig ileum.
IRL1620, a specific endothelin ETB receptor agonist, induced relaxation followed by contraction in the guinea-pig ileum, as did endothelin-1. Both components of the response were concentration-dependent in the range studied. Repeated administration of IRL1620 induced tachyphylaxis only of the contractile component, whereas endothelin-1 desensitized both components. BQ-123 (cyclo[D-Trp-D-Asp-Pro-D-Val-Leu]), a specific endothelin ETA receptor antagonist, did not inhibit the relaxation induced by either agonist, although it did inhibit the contraction induced by endothelin-1, but not by IRL1620. PD145065 (Ac-(D-Bhg-Leu-Asp-Ile-Ile-Trp) (D-Bhg = 5H-dibenzyl[a,d]cycloheptene-10,11-dihydroglycine)), a combined endothelin ETA/endothelin ETB receptor antagonist, inhibited the contractile effects of both endothelin-1 and IRL1620 and also inhibited the relaxation induced by IRL1620. Apamin, a Ca(2+)-activated K+ channel blocker, inhibited only the endothelin-1-induced relaxation. Our studies suggest that two endothelin ETB receptor subtypes mediate relaxation in the guinea-pig ileum: one is less sensitive to PD145065 but apamin-inhibitable, and the other is more sensitive to PD145065 but not apamin-inhibitable. Our results also suggest that both endothelin ETA and endothelin ETB receptor subtypes mediate contraction in the ileum.
Miasiro
N
N
Department of Biophysics, Escola Paulista de Medicina, São Paulo, Brazil.
Karaki
H
H
Paiva
A C
AC
D000595:Amino Acid Sequence; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000502:physiology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000502:physiology; D009126:Muscle Relaxation / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000819:agonists / Q000502:physiology*; D012964:Sodium / Q000378:metabolism
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D009842:Oligopeptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; C074308:sovateltide; C082887:PD 145065; D001030:Apamin; D012964:Sodium; C072247:cyclo(Trp-Asp-Pro-Val-Leu)