A REVERSIBLE RADIOLIGAND SPECIFIC FOR THE ET(B) RECEPTOR - [I-125] TYR13-SUC-[GLU9,ALA11,15]-ENDOTHELIN-1(8-21), [I-125] 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 t 1 2 of 100 min. This was in marked contrast to [125I] ET-3 which was hardly dissociated from the binding sites. © 1992.