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生长抑素及其类似物的生理

Author
Rodger A Liddle, MD
Section Editor
J Thomas Lamont, MD
Deputy Editor
Shilpa Grover, MD, MPH, AGAF
Translators
李昌平, 主任医师，教授

引言

生长抑素在胃肠道内分泌中扮演重要角色。最初发现其可抑制生长激素的释放[1]，现在认为它可以抑制多种胃肠道过程(表 1)[2]。生长抑素由整个胃肠道散在分布的旁分泌细胞产生，可抑制胃肠道内分泌。生长抑素也可见于多个神经系统部位，并通过神经控制许多生理功能。鉴于生长抑素具有多种作用，对其进行深入研究并不意外。生长抑素的合成类似物已被用于治疗一些临床疾病，如肢端肥大症、胃肠道激素分泌肿瘤和门脉高压性出血。

分子形式

生物活性生长抑素存在2种分子形式：生长抑素-14和生长抑素-28。两者都是前激素原翻译后加工的产物[3]。生长抑素是一种在进化过程中极为保守的环肽(图 1)。半胱氨酸残基之间的二硫键维持其环状结构。生长抑素-14与生长抑素-28羧基末端的14个氨基酸是相同的。生长抑素-14和生长抑素-28的生物活性存在于成熟肽的环状区域。受体占据需要环状结构的F-W-K-T部分。这个发现使得制造合成生物活性肽[如醋酸奥曲肽(SMS-201-995，Sandostatin)]成为可能(图 1)。

皮质抑素是一种结构上类似于生长抑素的神经肽，并可与所有生长抑素受体亚型结合。它也可以与生长激素促分泌素受体(growth hormone secretagogue receptor, GHS-R，也被称为食欲刺激素受体)相结合，但其生理功能尚不清楚[4]。

组织分布

生长抑素遍布于整个人体，但在皮质、下丘脑、脑干及脊髓等神经组织中尤其丰富。心脏、甲状腺、皮肤、眼和胸腺的神经中也已发现了生长抑素。胃肠道和胰腺富含生长抑素，这些部位通过旁分泌和内分泌样D细胞以及通过肠神经来产生生长抑素。整个胃肠道区域均可表达生长抑素-14和生长抑素-28。

生长抑素细胞形态多样。在胃肠道黏膜中，D细胞呈烧瓶形，含有长的胞浆突起，末端呈神经末梢样突起，随时准备着通过将激素释放入体循环或直接分泌至相邻细胞而参与内分泌调节。(参见“与健康和疾病相关的胃肠肽的概述”)这些细胞外形独特，似乎特别适合采集腔内容物样本并以旁分泌的方式影响局部细胞反应。在中枢和外周神经系统中，神经释放生长抑素起到肽能神经递质的作用。

           

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Literature review current through: 2017-06 . | This topic last updated: 2017-07-05.
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