Tayag E C, Jeng A Y, Savage P, Lehmann J C
Department of Neurosurgery, Medical College of Pennsylvania, Philadelphia 19102-1192, USA.
Eur J Pharmacol. 1996 Apr 11;300(3):261-5. doi: 10.1016/0014-2999(96)00004-0.
In most organs of the body, endothelin acts on endothelin ETA and ETB receptors that co-exist (albeit often on different cell types). Although virtually pure endothelin ETA receptors have been identified in some tissues (e.g., lung), no essentially pure endothelin ETB receptor tissue has been reported to date. [125I]Endothelin-1 bound to striatal membrane preparations with a Kd of 19.4 +/- 0.2 pM and Bmax of 496 +/- 8 fmol/mg protein. Endothelin-1 displaced [125I]endothelin-1 receptor binding with an IC50 of 23 pM. The endothelin ETB-selective antagonist BQ788 (N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma -methyl-leucyl-D-1-methoxycarbonyltryptophanyl-D-norleucine) and agonist sarafotoxin 6C displaced [125I]endothelin-1 monophasically with IC50 values of 25 nM and 110 pM, respectively, whereas that of the endothelin ETA-selective antagonist BQ123 (cyclo(D-Trp-D-Asp-Pro-D-Val-Leu)) was 24 microM, values agreeing with cloned human endothelin ETB but not ETA receptors. Receptor autoradiography confirmed that rat striatum (but not white matter) contains essentially exclusively endothelin ETB receptors.
在身体的大多数器官中，内皮素作用于共存的内皮素ETA和ETB受体（尽管它们常常存在于不同的细胞类型上）。虽然在一些组织（如肺）中已鉴定出几乎纯的内皮素ETA受体，但迄今为止尚未有基本上纯的内皮素ETB受体组织的报道。[125I]内皮素-1与纹状体膜制剂结合，解离常数（Kd）为19.4±0.2 pM，最大结合容量（Bmax）为496±8 fmol/mg蛋白质。内皮素-1以23 pM的半数抑制浓度（IC50）取代[125I]内皮素-1受体结合。内皮素ETB选择性拮抗剂BQ788（N-顺式-2,6-二甲基哌啶羰基-L-γ-甲基亮氨酰-D-1-甲氧基羰基色氨酰-D-正亮氨酸）和激动剂沙拉新6C分别以25 nM和110 pM的IC50值单相取代[125I]内皮素-1，而内皮素ETA选择性拮抗剂BQ123（环（D-色氨酸-D-天冬氨酸-脯氨酸-D-缬氨酸-亮氨酸））的IC50值为24 μM，这些值与克隆的人内皮素ETB受体而非ETA受体相符。受体放射自显影证实，大鼠纹状体（而非白质）基本上只含有内皮素ETB受体。
