title: Characterization of two new ETB selective radioligands, [125I]-BQ3020 and [125I]-[Ala1,3,11,15]ET-1 in human heart.
abstract: Two new endothelin receptor radioligands, [125I]-BQ3020 and [125I]-[Ala1,3,11,15]ET-1, were characterized in tissue sections of human right atrium and left ventricle. Both radioligands had high affinity ([125I]-BQ3020 right atrium: KD = 0.145 +/- 0.037 nM, left ventricle: KD = 0.107 +/- 0.004 nM; [125I]-[Ala1,3,11,15]ET-1 right atrium: KD = 0.239 +/- 0.036 nM, left ventricle: KD = 0.199 +/- 0.027 nM). Competition binding experiments were performed in the left ventricle. The selective ETA receptor compound BQ123 competed with low affinity against [125I]-BQ3020 (KD = 28.7 +/- 2.7 microM) and [125I]-[Ala1,3,11,15]ET-1 (KD = 28.5 +/- 4.2 microM). The selective ETB receptor compound BQ3020 competed with high affinity against [125I]-BQ3020 (KD = 40.8 +/- 6.6 pM) and [125I]-[Ala1,3,11,15]ET-1 (KD = 0.276 +/- 0.099 nM). Another selective ETB receptor compound, [Ala1,3,11,15]ET-1 also competed with high affinity against [125I]-BQ3020 (KD = 0.663 +/- 0.120 nM) and [125I]-[Ala1,3,11,15]ET-1 (KD = 0.643 +/- 0.124 nM). These results indicate that [125I]-BQ3020 and [125I]-[Ala1,3,11,15]ET-1 are selective ETB receptor radioligands. [Ala1,3,11,15]ET-1 competed with the non-selective radioligand [125I]-ET-1 in left ventricle and revealed the presence of ETA and ETB receptors in the proportions of 76:24% respectively in the human left ventricle.
authors: Clinical Pharmacology Unit, Addenbrooke's Hospital, Cambridge.
authors: P
authors: P
authors: Molenaar
authors: R E
authors: RE
authors: Kuc
authors: A P
authors: AP
authors: Davenport
mesh_terms: D001667:Binding, Competitive / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology*; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008024:Ligands; D009206:Myocardium / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology
chemical_list: D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007457:Iodine Radioisotopes; D008024:Ligands; D010446:Peptide Fragments; D010456:Peptides, Cyclic; C061779:endothelin 1, Ala(1,3,11,15)-; C075771:BQ 3020; C072247:cyclo(Trp-Asp-Pro-Val-Leu)