生长激素抑制素及其受体家族。

文章的细节

引用

复制到剪贴板

帕特尔YC

生长激素抑制素及其受体家族。

Neuroendocrinol前面。1999年7月,20 (3):157 - 98。

PubMed ID

10433861 (在PubMed

]

文摘

监管肽生长抑素(SST),是由神经内分泌,炎症,免疫细胞反应离子,营养,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。肽释放大量的存储池的分泌细胞,或少量激活免疫和炎症细胞和作为内源性抑制调节器的分泌和增生性反应的靶细胞广泛分布在大脑和外围。这些行动是由一个家庭的七个跨膜域(TM) G-protein-coupled组成五个不同受体亚型(称为SSTR1-5) endoded单独隔离不同染色体上的基因。五个受体亚型结合自然SST肽SST-14 SST-28,摩尔亲和力较低。短的合成八肽和hexapeptide类似物结合只有三个亚型,2,3,5。选择性nonpeptide与摩尔亲和力的受体激动剂开发的四个亚型(SSTR1 2、3和4)和假定的肽拮抗剂SSTR2和SSTR5已确定。海温配体配体结合域是由残留在TMs III-VII第二个细胞外循环的潜在贡献。SSTRs是在许多组织中广泛表达,经常作为多个亚型,位于相同的单元中共存。等五个共同受体信号通路抑制腺苷酸环化酶的激活phosphotyrosine磷酸酶(PTP)和调制增殖作用的蛋白激酶(MAPK)通过G-protein-dependent机制。一些亚型也耦合的内向整流K(+)渠道(SSTR2, 3、4、5),压敏电阻器Ca(2 +)频道(SSTR1, 2),钠(+)/ H(+)换热器(SSTR1), AMPA / kainate谷氨酸通道(SSTR1, 2),磷脂酶C (SSTR2 5)和磷脂酶(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).

DrugBank数据引用了这篇文章

药物

生长激素抑制素