Functionally distinct endothelin B receptors in vascular endothelium and smooth muscle.
IRL 1620 (Suc-[Glu9,Ala11,15]-ET-1 (8-21)) (0.1 nM - 1 microM), a novel ETB-selective endothelin (ET) agonist, produced endothelium-dependent relaxations in precontracted rabbit mesenteric artery (2 nM, EC50) and endothelium-independent contractions in porcine coronary artery (18 nM, EC50). ET-3 (0.1 nM-10 nM) produced qualitatively similar responses in the two tissues. The maximal contractions induced by IRL 1620 or ET-3 were substantially smaller (< 20%) than that produced by ET-1. BQ-123 (1 microM), an ETA receptor antagonist, inhibited responses to ET-1 without affecting IRL 1620- or ET-3-induced responses in either tissue. Thus functionally distinct ETB receptors mediating vasodilator and vasoconstrictor effects are located on the vascular endothelium and smooth muscle, respectively. The overall effect of ETB receptor activation on vascular tone is tissue-specific and presumably reflects differing receptor distribution at the two sites.
Shetty
S S
SS
Research Department, Pharmaceuticals Division, CIBA-GEIGY Corp., Summit, NJ 07901.
Okada
T
T
Webb
R L
RL
DelGrande
D
D
Lappe
R W
RW
D000818:Animals; D001665:Binding Sites; D016232:Endothelins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology; D011817:Rabbits; D017466:Receptors, Endothelin / Q000378:metabolism*; D013552:Swine
D016232:Endothelins; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; C074308:sovateltide; C072247:cyclo(Trp-Asp-Pro-Val-Leu)