A novel ligand, [125I]BQ-3020, reveals the localization of endothelin ETB receptors.
The precise localization of an endothelin (ET) receptor subtype, the ETB receptor, in porcine lung was elucidated by in vitro microautoradiography using a novel ETB-selective radioligand, [125I]BQ-3020 ([125I-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, [125I]ET-3 is selective for ETB receptors. However, [125I]ET-3 was not suitable for autoradiography due to its high degree of non-specific binding. On the other hand, [125I]BQ-3020 showed extremely low non-specific binding on autoradiography. The distribution of [125I]BQ-3020 binding in porcine lung was clearly different from that of [125I]ET-1, which showed more widespread binding than [125I]BQ-3020 due to a high affinity to both ETA and ETB receptors. [125I]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 [125I]ET-1 bound to the smooth muscle layer of all blood vessels, the binding of [125I]BQ-3020 differed among blood vessels. [125I]BQ-3020 binding in blood vessels paralleled acetylcholinesterase activity, suggesting that ETB receptors in blood vessels are located on parasympathetic nerves. Thus, the radioligand [125I]BQ-3020 is very useful for studying the precise localization of ETB receptors.
Kobayashi
M
M
Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Japan.
Ihara
M
M
Sato
N
N
Saeki
T
T
Ozaki
S
S
Ikemoto
F
F
Yano
M
M
D000110:Acetylcholinesterase / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001808:Blood Vessels / Q000378:metabolism; D016232:Endothelins / Q000737:chemistry / Q000378:metabolism*; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D017466:Receptors, Endothelin / Q000378:metabolism*; D013552:Swine
D016232:Endothelins; D010446:Peptide Fragments; D017466:Receptors, Endothelin; C075771:BQ 3020; D000110:Acetylcholinesterase