两种新型ETB选择性放射性配体[125I]-BQ3020和[125I]-[丙氨酸1,3,11,15]ET-1在人心脏中的特性研究
Characterization of two new ETB selective radioligands, [125I]-BQ3020 and [125I]-[Ala1,3,11,15]ET-1 in human heart.
作者信息
Molenaar P, Kuc R E, Davenport A P
机构信息
Clinical Pharmacology Unit, Addenbrooke's Hospital, Cambridge.
出版信息
Br J Pharmacol. 1992 Nov;107(3):637-9. doi: 10.1111/j.1476-5381.1992.tb14498.x.
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.
两种新的内皮素受体放射性配体，即[125I]-BQ3020和[125I]-[丙氨酸1,3,11,15]ET-1，在人右心房和左心室组织切片中进行了特性研究。两种放射性配体都具有高亲和力（[125I]-BQ3020在右心房：KD = 0.145±0.037 nM，在左心室：KD = 0.107±0.004 nM；[125I]-[丙氨酸1,3,11,15]ET-1在右心房：KD = 0.239±0.036 nM，在左心室：KD = 0.199±0.027 nM）。在左心室进行了竞争结合实验。选择性ETA受体化合物BQ123以低亲和力与[125I]-BQ3020（KD = 28.7±2.7 microM）和[125I]-[丙氨酸1,3,11,15]ET-1（KD = 28.5±4.2 microM）竞争。选择性ETB受体化合物BQ3020以高亲和力与[125I]-BQ3020（KD = 40.8±6.6 pM）和[125I]-[丙氨酸1,3,11,15]ET-1（KD = 0.276±0.099 nM）竞争。另一种选择性ETB受体化合物，[丙氨酸1,3,11,15]ET-1也以高亲和力与[125I]-BQ3020（KD = 0.663±0.120 nM）和[125I]-[丙氨酸1,3,11,15]ET-1（KD = 0.643±0.124 nM）竞争。这些结果表明，[125I]-BQ3020和[125I]-[丙氨酸1,3,11,15]ET-1是选择性ETB受体放射性配体。[丙氨酸1,3,11,15]ET-1在左心室与非选择性放射性配体[125I]-ET-1竞争，并揭示了人左心室中ETA和ETB受体的比例分别为76:24%。
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