A NOVEL LIGAND, [I-125] BQ-3020, REVEALS THE LOCALIZATION OF ENDOTHELIN-ET(B) RECEPTORS

The precise localization of an endothelin (ET) receptor subtype, the E T(B) receptor, in porcine lung was elucidated by in vitro microautorad iography using a novel ET(B)-selective radioligand, [I-125]BQ-3020 -Gl u-Ala-Val-Tyr-Phe-Ala-His-Leu-Asp-Ile-Ile-Trp). Of the labeled native ET isopeptides, [I-125]ET-3 is selective for ET(B) receptors. However, [I-125]ET-3 was not suitable for autoradiography due to its high degr ee of non-specific binding. On the other hand, [I-125]BQ-3020 showed e xtremely low non-specific binding on autoradiography. The distribution of [I-125]BQ-3020 binding in porcine lung was clearly different from that of [I-125]ET-1, which showed more widespread binding than [I-125] BQ-3020 due to a high affinity to both ET(A) and ET(B) receptors. [I-1 25]BQ-3020 was found to bind to parenchyma, parasympathetic ganglia, p ulmonary and submucosal plexuses, but bound only slightly to circular smooth muscle layers and the epithelium of airway tracts. Although [I- 125]ET-1 bound to the smooth muscle layer of all blood vessels, the bi nding of [I-125]BQ-3020 differed among blood vessels. [I-125]BQ-3020 b inding in blood vessels paralleled acetylcholinesterase activity, sugg esting that ET(B) receptors in blood vessels are located on parasympat hetic nerves. Thus, the radioligand [I-125]BQ-3020 is very useful for studying the precise localization of ET(B) receptors.