Ferjoux G, Bousquet C, Cordelier P, Benali N, Lopez F, Rochaix P, Buscail L, Susini C
Inserm U 151, CHU Rangueil, IFR 31, Toulouse, France.
J Physiol Paris. 2000 May-Aug;94(3-4):205-10. doi: 10.1016/s0928-4257(00)00206-0.
Somatostatin acts as an inhibitory peptide of various secretory and proliferative responses. Its effects are mediated by a family of G-protein-coupled receptors (sst1-5) that can couple to diverse signal transduction pathways such as inhibition of adenylate cyclase and guanylate cyclase, modulation of ionic conductance channels, and protein dephosphorylation. The five receptors bind the natural peptide with high affinity but only sst2, sst5 and sst3 bind the short synthetic analogues. Somatostatin negatively regulates the growth of various normal and tumour cells. This effect is mediated indirectly through inhibition of secretion of growth-promoting factors, angiogenesis and modulation of the immune system. Somatostatin can also act directly through sst receptors present on target cells. The five receptors are expressed in various normal and tumour cells, the expression of each receptor being receptor subtype and cell type specific. According to the receptor subtypes, distinct signal transduction pathways are involved in the antiproliferative action of somatostatin. Sst1, 4 and 5 modulate the MAP kinase pathway and induce G1 cell cycle arrest. Sst3 and sst2 promote apoptosis by p53-dependent and -independent mechanisms, respectively.
生长抑素作为一种对多种分泌和增殖反应起抑制作用的肽。其作用由一类G蛋白偶联受体（sst1 - 5）介导，这些受体可与多种信号转导途径偶联，如抑制腺苷酸环化酶和鸟苷酸环化酶、调节离子传导通道以及蛋白质去磷酸化。这五种受体以高亲和力结合天然肽，但只有sst2、sst5和sst3结合短的合成类似物。生长抑素对多种正常细胞和肿瘤细胞的生长起负调节作用。这种作用通过抑制促生长因子的分泌、血管生成以及调节免疫系统间接介导。生长抑素也可通过靶细胞上存在的sst受体直接发挥作用。这五种受体在多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。根据受体亚型，生长抑素的抗增殖作用涉及不同的信号转导途径。Sst1、4和5调节丝裂原活化蛋白激酶（MAP）途径并诱导G1期细胞周期停滞。Sst3和sst2分别通过依赖p53和不依赖p53的机制促进细胞凋亡。
