Cholecystokinin-From Local Gut Hormone to Ubiquitous Messenger.
Cholecystokinin-From Local Gut Hormone to Ubiquitous Messenger.
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DOI：
10.3389/fendo.2017.00047
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发表时间：
2017
影响因子：
5.2
通讯作者：
Rehfeld JF
中科院分区：
文献类型：
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作者：
Rehfeld JF
胆囊收缩素(CCK)是1928年在空肠提取液中发现的一种胆囊收缩因子。后来发现它是一个多肽家族的成员，这些多肽都是CCK1和CCK2受体的配体。已知CCK多肽在小肠内分泌I细胞和大脑神经元中合成。但除此之外，CCK在几个内分泌腺(垂体细胞、甲状腺C细胞、胰岛、肾上腺和睾丸)、外周神经、皮质和髓质肾细胞、心肌细胞和免疫系统细胞中都有表达。CCK多肽可刺激胰酶分泌和生长、胆囊壁收缩、肠道运动、饱腹感和抑制胃酸分泌。此外，它们是大脑和外周的主要神经递质。CCK多肽还可以刺激降钙素、胰岛素和胰升糖素的分泌，它们可能在肾脏中起到利钠肽的作用。CCK多肽是由ProCCK衍生而来，具有C-末端生物活性的YMGWMDFamide序列，其中Y-残基部分O-硫化。血浆形式为CCK-58、-33、-22和-8，而小的CCK-8和-5是有效的神经递质。在过去的几十年里，CCK在肿瘤(神经内分泌瘤、脑星形细胞瘤、胶质瘤、听神经瘤和特定的儿科肿瘤)中也有表达。最近，一种转移性胰岛细胞瘤被发现引起一种特殊的CCKoma综合征，提示循环CCK可能是一种有用的肿瘤标志物。
Cholecystokinin (CCK) was discovered in 1928 in jejunal extracts as a gallbladder contraction factor. It was later shown to be member of a peptide family, which are all ligands for the CCK1 and CCK2 receptors. CCK peptides are known to be synthetized in small intestinal endocrine I-cells and cerebral neurons. But in addition, CCK is expressed in several endocrine glands (pituitary cells, thyroid C-cells, pancreatic islets, the adrenals, and the testes); in peripheral nerves; in cortical and medullary kidney cells; in cardial myocytes; and in cells of the immune system. CCK peptides stimulate pancreatic enzyme secretion and growth, gallbladder contraction, and gut motility, satiety and inhibit acid secretion from the stomach. Moreover, they are major neurotransmitters in the brain and the periphery. CCK peptides also stimulate calcitonin, insulin, and glucagon secretion, and they may act as natriuretic peptides in the kidneys. CCK peptides are derived from proCCK with a C-terminal bioactive YMGWMDFamide sequence, in which the Y-residue is partly O-sulfated. The plasma forms are CCK-58, -33, -22, and -8, whereas the small CCK-8 and -5 are potent neurotransmitters. Over the last decades, CCK expression has also been encountered in tumors (neuroendocrine tumors, cerebral astrocytomas, gliomas, acoustic neuromas, and specific pediatric tumors). Recently, a metastastic islet cell tumor was found to cause a specific CCKoma syndrome, suggesting that circulating CCK may be a useful tumor marker.