Benali N, Ferjoux G, Puente E, Buscail L, Susini C
INSERM U 531, CHU Rangueil, Toulouse, France.
Digestion. 2000;62 Suppl 1:27-32. doi: 10.1159/000051852.
Somatostatin is a neuropeptide produced by neuroendocrine, inflammatory and immune cells in response to different stimuli. Somatostatin inhibits various cellular functions including secretions, motility and proliferation. Its action is mediated by five specific somatostatin receptors (sst1-sst5) which belong to the G protein-coupled receptor family. The five receptors bind the natural peptide with high affinity but only sst2, sst5 and sst3 bind the short synthetic analogues used to treat patients with neuroendocrine tumors. The five receptors are expressed in various normal and tumor cells, the expression of each receptor being receptor subtype and cell-type specific. In neuroendocrine tumors, sst2 is highly expressed whereas in advanced pancreatic adenocarcinoma as well as high-grade colorectal carcinomas, its expression is lost. Each receptor subtype is coupled to different signal transduction pathways through G protein-dependent and -independent mechanisms. The synthesis of selective agonists for each receptor and the recent development of genetic animal models with selective deletion of receptor subtype provide tools for establishing some of the biological roles of the receptors. sst1, 2 and 5 mediate inhibition of GH secretion whereas sst2 and sst5 mediate inhibition of glucagon secretion and insulin secretion, respectively.
生长抑素是一种神经肽，由神经内分泌细胞、炎症细胞和免疫细胞在不同刺激下产生。生长抑素抑制包括分泌、运动和增殖在内的各种细胞功能。其作用由五种特异性生长抑素受体（sst1 - sst5）介导，这些受体属于G蛋白偶联受体家族。这五种受体以高亲和力结合天然肽，但只有sst2、sst5和sst3结合用于治疗神经内分泌肿瘤患者的短合成类似物。这五种受体在各种正常细胞和肿瘤细胞中表达，每种受体的表达具有受体亚型和细胞类型特异性。在神经内分泌肿瘤中，sst2高度表达，而在晚期胰腺腺癌以及高级别结直肠癌中，其表达缺失。每种受体亚型通过G蛋白依赖性和非依赖性机制与不同的信号转导途径偶联。针对每种受体的选择性激动剂的合成以及最近具有受体亚型选择性缺失的基因动物模型的开发，为确定这些受体的一些生物学作用提供了工具。sst1、2和5介导生长激素分泌的抑制，而sst2和sst5分别介导胰高血糖素分泌和胰岛素分泌的抑制。
