TY - JOUR
T1 - Endothelin ETB receptor antagonist, RES-701-1
T2 - effects on isolated blood vessels and small intestine
AU - Karaki, Hideaki
AU - Sudjarwo, Sri Agus
AU - Hori, Masatoshi
AU - Tanaka, Takeo
AU - Matsuda, Yuzuru
N1 - Funding Information:
We are grateful to Drs. A.F. James and T. Okada, Ciba Geigy (Japan), for useful discussion and critical reading of the manuscript. This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, Japan.
PY - 1994/9/12
Y1 - 1994/9/12
N2 - RES-701-1 (cyclic (Gly1Asp9)(GlyAsnTrpHisGlyThrAlaProAspTrp PhePheAsnTyrTyrTrp)), 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 μM 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 μM 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 μM RES-701-1. In the norepinephrine-stimulated aorta, endothelium-dependent relaxation induced by endothelin-3 was antagonized by 0.3-10 μM 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 μM) 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.
AB - RES-701-1 (cyclic (Gly1Asp9)(GlyAsnTrpHisGlyThrAlaProAspTrp PhePheAsnTyrTyrTrp)), 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 μM 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 μM 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 μM RES-701-1. In the norepinephrine-stimulated aorta, endothelium-dependent relaxation induced by endothelin-3 was antagonized by 0.3-10 μM 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 μM) 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.
KW - EDRF (endothelium-derived relaxing factor)
KW - Endothelin
KW - Endothelin ET receptor
KW - Endothelin ET receptor antagonist
KW - RES-701-1
KW - Smooth muscle
UR - http://www.scopus.com/inward/record.url?scp=0028170097&partnerID=8YFLogxK
U2 - 10.1016/0014-2999(94)90739-0
DO - 10.1016/0014-2999(94)90739-0
M3 - Article
C2 - 7813590
AN - SCOPUS:0028170097
SN - 0014-2999
VL - 262
SP - 255
EP - 259
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 3
ER -