A reversible radioligand specific for the ETB receptor: [125I]Tyr13-Suc-[Glu9,Ala11,15]-endothelin-1(8- 21), [125I]IRL 1620.
Suc-[Glu9,Ala11,15]-endothelin(ET)-1(8-21), IRL 1620, is a linear ET-analog specific for the ET-isopeptide-nonselective ETB receptor. The radio-iodinated analog, [125I]IRL 1620, showed a single class of saturable binding to the ETB receptors in porcine lung membranes with a Kd of 18 pM and a Bmax of 930 fmol/mg protein, which are almost comparable to the values obtained with [125I]ET-3 (6 pM and 900 fmol/mg protein). In competitive binding assays with [125I]IRL 1620, unlabeled ET-1, ET-3, IRL 1620 and [monoiodo-Tyr13]-IRL 1620 showed almost identical displacement curves with Ki of 8 to 16 pM. However, [125I]IRL 1620 was dissociated from the binding sites by addition of an excess amount (100 nM) of any of these unlabeled peptides, each with the same t1/2 of 100 min. This was in marked contrast to [125I]ET-3 which was hardly dissociated from the binding sites.
Watakabe
T
T
International Research Laboratories, CIBA-GEIGY (Japan), Ltd., Takarazuka.
Urade
Y
Y
Takai
M
M
Umemura
I
I
Okada
T
T
D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D016232:Endothelins / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017466:Receptors, Endothelin; D013552:Swine
D016232:Endothelins; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; C074308:sovateltide