A novel ligand, [125I]BQ-3020, reveals the localization of endothelin ETB receptors

Abstract The precise localization of an endothelin (ET) receptor subtype, the ET B receptor, in porcine lung was elucidated by in vitro microautoradiography using a novel ET B -selective radioligand, [ 125 I]BQ-3020 ([ 125 I-Tyr]-N-acetyl-Leu-Met-Asp-Lys-Glu-Ala-Val- Tyr-Phe-Ala-His-Leu-Asp-Ile-Ile-Trp). Of the labeled native ET isopeptides, [ 125 I]ET-3 is selective for ET B receptors. However, [ 125 I]ET-3 was not suitable for autoradiography due to its high degree of non-specific binding. On the other hand, [ 125 I]BQ-3020 showed extremely low non-specific binding on autoradiography. The distribution of [ 125 I]BQ-3020 binding in porcine lung was clearly different from that of [ 125 I]ET-1, which showed more widespread binding than [ 125 I]BQ-3020 due to a high affinity to both ET A and ET B receptors. [ 125 I]BQ-3020 was found to bind to parenchyma, parasympathetic ganglia, pulmonary and submucosal plexuses, but bound only slightly to circular smooth muscle layers and the epithelium of airway tracts. Although [ 125 I]ET-1 bound to the smooth muscle layer of all blood vessels, the binding of [ 125 I]BQ-3020 differed among blood vessels. [ 125 I]BQ-3020 binding in blood vessels paralleled acetylcholinesterase activity, suggesting that ET B receptors in blood vessels are located on parasympathetic nerves. Thus, the radioligand [ 125 I]BQ-3020 is very useful for studying the precise localization of ET B receptors.