Characterization of two new ETB selective radioligands, [125I]‐BQ3020 and [125I]‐[Ala1,3,11,15]ET‐1 in human heart

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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 μm) and [125I]-[Ala1,3,11,15]ET-1 (KD = 28.5 ± 4.2 μm). 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-l (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.