A potent and specific agonist, Suc-[Glu9,Ala11,15]-endothelin-1(8-21), IRL 1620, for the ETB receptor.
A series of C-terminal linear peptides of endothelin (ET)-1 and their N alpha-succinyl (Suc) analogs were synthesized and their binding affinities for the two subtypes of ET receptor, ETA and ETB, in porcine lung membranes were examined. Among the synthetic analogs, Suc-[Glu9,Ala11,15]-ET-1(8-21), IRL 1620, was the most potent and specific ligand for the ETB receptor (KiETA/KiETB approximately equal to 120,000) as judged by the Ki values for ETA (1.9 microM) and ETB (16 pM) receptors. IRL 1620 was 60 times more selective for the ETB receptor than ET-3 (KiETA/KiETB approximately equal to 1,900). IRL 1620 (10(-9)-10(-7) M) induced contractions of the guinea pig trachea with a comparable potency to those of ET-1 or ET-3, suggesting that IRL 1620 is a potent ETB receptor agonist.
Takai
M
M
International Research Laboratories, CIBA-GEIGY Ltd., Takarazuka, Japan.
Umemura
I
I
Yamasaki
K
K
Watakabe
T
T
Fujitani
Y
Y
Oda
K
K
Urade
Y
Y
Inui
T
T
Yamamura
T
T
Okada
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D016232:Endothelins / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D017466:Receptors, Endothelin; D013329:Structure-Activity Relationship; D013552:Swine; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D016232:Endothelins; D010446:Peptide Fragments; D010455:Peptides; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; C074308:sovateltide