Lysko P G, Webb C L, Feuerstein G
Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA.
Peptides. 1995;16(7):1279-82. doi: 10.1016/0196-9781(95)00096-3.
We studied the binding characteristics of a novel, nonpeptide endothelin antagonist, SB 209670, to two subtypes of endothelin (ET) receptor in cultured rat cerebellar granule cell neurons. Displacement binding studies of [125I]ET-1 performed in the presence of the ETB receptor-selective agonist, sarafotoxin 6c (S6c), allowed us to measure a Ki of 4.0 +/- 1.5 nM for (+/-)SB 209670 at the ETA receptor (n = 4). Similarly, binding studies in the presence of the ETA receptor-selective antagonist, BQ123, allowed us to measure a Ki of 46 +/- 14 nM for (+/-)SB 209670 at the ETB receptor (n = 4). These studies indicate that the novel endothelin antagonist, SB 209670, has high affinity for both types of neuronal endothelin receptor.
我们研究了一种新型非肽类内皮素拮抗剂SB 209670与培养的大鼠小脑颗粒细胞神经元中两种亚型内皮素（ET）受体的结合特性。在ETB受体选择性激动剂沙拉新（S6c）存在的情况下进行的[125I]ET-1置换结合研究，使我们能够测得（±）SB 209670在ETA受体上的Ki为4.0±1.5 nM（n = 4）。同样，在ETA受体选择性拮抗剂BQ123存在的情况下进行的结合研究，使我们能够测得（±）SB 209670在ETB受体上的Ki为46±14 nM（n = 4）。这些研究表明，新型内皮素拮抗剂SB 209670对两种类型的神经元内皮素受体均具有高亲和力。
