Endothelin ETB receptor antagonist, RES-701-1: effects on isolated blood vessels and small intestine.
RES-701-1 (cyclic (Gly1-Asp9)(Gly-Asn-Trp-His-Gly-Thr-Ala-Pro-Asp-Trp-Phe- Phe-Asn-Tyr-Tyr-Trp)), a peptide isolated from Streptomyces sp., has been reported to inhibit the endothelin ETB receptor. We examined the effects of this peptide on the blood vessels and the small intestine. In isolated rat aorta without endothelium, 10 microM RES-701-1 did not affect the resting tone, nor did it attenuate the contractions induced by endothelin-1, endothelin-3 or norepinephrine. In the aorta with endothelium, 3 microM RES-701-1 shifted the concentration-response curves for the contractile effects of endothelin-1 and endothelin-3 to the left. Removal of endothelium showed a similar effect to 3 microM RES-701-1. In the norepinephrine-stimulated aorta, endothelium-dependent relaxation induced by endothelin-3 was antagonized by 0.3-10 microM RES-701-1 in a concentration-dependent manner. In the guinea pig ileum stimulated by carbachol, endothelin-3 induced a transient relaxation followed by sustained relaxation. RES-101-1 (3 microM) selectively inhibited the transient relaxation. Since it has been shown that the contractile effects of endothelins in the aorta are mediated by the endothelin ETA receptor whereas the endothelium-dependent relaxation and the ileal relaxation are mediated by the endothelin ETB receptor, it is suggested that RES-701-1 is a selective antagonist against the endothelin ETB receptor.
Karaki
H
H
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Science, University of Tokyo, Japan.
Sudjarwo
S A
SA
Hori
M
M
Tanaka
T
T
Matsuda
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology; D006168:Guinea Pigs; D007421:Intestine, Small / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044023:Receptor, Endothelin B
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; D044023:Receptor, Endothelin B; C087120:RES 701-1; D002217:Carbachol; D009638:Norepinephrine