Siehler S, Seuwen K, Hoyer D
Nervous System Research, Novartis Pharma AG, Basel, Switzerland.
Naunyn Schmiedebergs Arch Pharmacol. 1998 May;357(5):483-9. doi: 10.1007/pl00005197.
The recently cloned rat preprocortistatin, which shows homology to the preprosomatostatin peptide, is thought to be enzymatically cleaved to cortistatin14 (CST14) similarly to somatostatin14 (SRIF14). High structural similarity of cortistatin14 compared to SRIF14 suggested binding properties to somatostatin receptors similar to SRIF14. In the present study, we expressed stably the five human somatostatin receptor subtypes (hsst1-hsst5) in CCL39 cells (Chinese hamster lung fibroblast cells). The receptors were labelled with an iodinated analogue of CST14 ([125I]Tyr10)-cortistatin14, [125I]Tyr10-CST) to establish the pharmacological profile of hsst1-hsst5 sites labelled with [125I]Tyr10-CST. In parallel, [Leu8,D-Trp22,125I-Tyr25]-SRIF28 ([125I]LTT-SRIF28) was used as a control at the five recombinant SRIF receptors stably expressed in CCL39 cells. High affinity [125I]Tyr10-CST binding could be demonstrated to all five recombinant somatostatin receptor subtypes. The pKd (-log mol/l) and Bmax values (fmol/mg) for hsst1-5 receptors were: 10.02+/-0.04, 220+/-30; 9.45+/-0.09, 340+/-70; 10.06+/-0.11, 340+/-50; 9.67+/-0.14, 340+/-110 and 10.33+/-0.03, 5630+/-1330, respectively. The pharmacological profiles determined with [125I]Tyr10-CST and [125I]LTT-SRIF28 were very similar at every receptor studied. These data suggest that cortistatin and somatostatin have similar high affinity for SRIF receptors. None of the receptors showed marked selectivity for either CST14/CST17 or the somatostatins. In conclusion, the data show that cortistatin and somatostatin have very similar high affinity to all five recombinant somatostatin receptors. It remains to be seen whether there are specific receptors which bind only somatostatins or cortistatins.
最近克隆的大鼠前体促皮质素原与前体生长抑素肽具有同源性，据认为它会像生长抑素14（SRIF14）一样被酶解为促皮质素14（CST14）。与SRIF14相比，促皮质素14具有高度的结构相似性，这表明它与生长抑素受体的结合特性类似于SRIF14。在本研究中，我们在CCL39细胞（中国仓鼠肺成纤维细胞）中稳定表达了五种人类生长抑素受体亚型（hsst1 - hsst5）。用促皮质素14的碘化类似物（[125I]Tyr10） - 促皮质素14，即[125I]Tyr10 - CST对这些受体进行标记，以建立用[125I]Tyr10 - CST标记的hsst1 - hsst5位点的药理学特征。同时，[Leu8，D - Trp22，125I - Tyr25] - SRIF28（[125I]LTT - SRIF28）被用作在CCL39细胞中稳定表达的五种重组SRIF受体的对照。结果表明，[125I]Tyr10 - CST对所有五种重组生长抑素受体亚型均具有高亲和力结合。hsst1 - 5受体的pKd（-log mol/l）和Bmax值（fmol/mg）分别为：10.02±0.04，220±30；9.45±0.09，340±70；10.06±0.11，340±50；9.67±0.14，340±110和10.33±0.03，5630±1330。在用[125I]Tyr10 - CST和[125I]LTT - SRIF28测定的药理学特征中，在所研究的每种受体上都非常相似。这些数据表明，促皮质素和生长抑素对SRIF受体具有相似的高亲和力。没有一种受体对CST14/CST17或生长抑素表现出明显的选择性。总之，数据表明促皮质素和生长抑素对所有五种重组生长抑素受体具有非常相似的高亲和力。是否存在仅结合生长抑素或促皮质素的特异性受体还有待观察。
