...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Frontiers in neuroendocrinology >Somatostatin and its receptor family.
【24h】

Somatostatin and its receptor family.

机译：生长抑素及其受体家族。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Somatostatin (SST), a regulatory peptide, is produced by neuroendocrine, inflammatory, and immune cells in response to ions, nutrients, neuropeptides, neurotransmitters, thyroid and steroid hormones, growth factors, and cytokines. The peptide is released in large amounts from storage pools of secretory cells, or in small amounts from activated immune and inflammatory cells, and acts as an endogenous inhibitory regulator of the secretory and proliferative responses of target cells that are widely distributed in the brain and periphery. These actions are mediated by a family of seven transmembrane (TM) domain G-protein-coupled receptors that comprise five distinct subtypes (termed SSTR1-5) that are endoded by separate genes segregated on different chromosomes. The five receptor subtypes bind the natural SST peptides, SST-14 and SST-28, with low nanomolar affinity. Short synthetic octapeptide and hexapeptide analogs bind well to only three of the subtypes, 2, 3, and 5. Selective nonpeptide agonists with nanomolar affinity have been developed for four of the subtypes (SSTR1, 2, 3, and 4) and putative peptide antagonists for SSTR2 and SSTR5 have been identified. The ligand binding domain for SST ligands is made up of residues in TMs III-VII with a potential contribution by the second extracellular loop. SSTRs are widely expressed in many tissues, frequently as multiple subtypes that coexist in the same cell. The five receptors share common signaling pathways such as the inhibition of adenylyl cyclase, activation of phosphotyrosine phosphatase (PTP), and modulation of mitogen-activated protein kinase (MAPK) through G-protein-dependent mechanisms. Some of the subtypes are also coupled to inward rectifying K(+) channels (SSTR2, 3, 4, 5), to voltage-dependent Ca(2+) channels (SSTR1, 2), a Na(+)/H(+) exchanger (SSTR1), AMPA/kainate glutamate channels (SSTR1, 2), phospholipase C (SSTR2, 5), and phospholipase A(2) (SSTR4). SSTRs block cell secretion by inhibiting intracellular cAMP and Ca(2+) and by a receptor-linked distal effect on exocytosis. Four of the receptors (SSTR1, 2, 4, and 5) induce cell cycle arrest via PTP-dependent modulation of MAPK, associated with induction of the retinoblastoma tumor suppressor protein and p21. In contrast, SSTR3 uniquely triggers PTP-dependent apoptosis accompanied by activation of p53 and the pro-apoptotic protein Bax. SSTR1, 2, 3, and 5 display acute desensitization of adenylyl cyclase coupling. Four of the subtypes (SSTR2, 3, 4, and 5) undergo rapid agonist-dependent endocytosis. SSTR1 fails to be internalized but is instead upregulated at the membrane in response to continued agonist exposure. Among the wide spectrum of SST effects, several biological responses have been identified that display absolute or relative subtype selectivity. These include GH secretion (SSTR2 and 5), insulin secretion (SSTR5), glucagon secretion (SSTR2), and immune responses (SSTR2). Copyright 1999 Academic Press.
机译：生长抑素（SST）是一种调节肽，由神经内分泌，炎症和免疫细胞响应离子，营养素，神经肽，神经递质，甲状腺和类固醇激素，生长因子和细胞因子而产生。该肽从分泌细胞的储存池中大量释放，或从活化的免疫和炎性细胞中少量释放，并作为广泛分布于大脑和外周的靶细胞分泌和增殖反应的内源性抑制调节剂。 。这些作用由七个跨膜（TM）域G蛋白偶联受体家族介导，该受体包含五个不同的亚型（称为SSTR1-5），这些亚型由分离在不同染色体上的独立基因所赋予。五个受体亚型以低纳摩尔亲和力结合天然SST肽SST-14和SST-28。短的合成八肽和六肽类似物仅与两种亚型2、2、3和5良好结合SSTR2和SSTR5的标识已被确定。 SST配体的配体结合结构域由TMs III-VII中的残基组成，第二个细胞外环可能具有潜在作用。 SSTRs在许多组织中广泛表达，通常是在同一细胞中共存的多种亚型。这五个受体具有共同的信号通路，例如抑制腺苷酸环化酶，激活磷酸酪氨酸磷酸酶（PTP）和通过G蛋白依赖性机制调节促分裂原活化的蛋白激酶（MAPK）。一些亚型还与向内整流K（+）通道（SSTR2、3、4、5），与电压相关的Ca（2+）通道（SSTR1、2），Na（+）/ H（+ ）交换剂（SSTR1），AMPA /海藻酸谷氨酸通道（SSTR1、2），磷脂酶C（SSTR2、5）和磷脂酶A（2）（SSTR4）。 SSTR通过抑制细胞内cAMP和Ca（2+）并通过胞外作用的受体相关的远端效应来阻止细胞分泌。四个受体（SSTR1、2、4和5）通过PTP依赖的MAPK调节来诱导细胞周期停滞，这与视网膜母细胞瘤肿瘤抑制蛋白和p21的诱导有关。相反，SSTR3独特地触发PTP依赖性凋亡，并激活p53和促凋亡蛋白Bax。 SSTR1、2、3和5显示腺苷酸环化酶偶联的急性脱敏。亚型中的四个（SSTR2、3、4和5）经历了激动剂依赖性快速内吞作用。 SSTR1不能被内在化，而是响应于持续的激动剂暴露而在膜上调。在广泛的SST效应中，已鉴定出几种显示绝对或相对亚型选择性的生物学反应。这些包括GH分泌（SSTR2和5），胰岛素分泌（SSTR5），胰高血糖素分泌（SSTR2）和免疫应答（SSTR2）。版权所有1999 Academic Press。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号