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荷兰十年胆囊收缩素放射免疫分析经验

A decade of experiences with radioimmunoassays for cholecystokinin in The Netherlands.

作者信息

Jansen J B, Hopman W P, Lamers C B

机构信息

Dept. of Gastroenterology, University Hospital, Nijmegen, The Netherlands.

出版信息

Scand J Gastroenterol Suppl. 1992;194:47-54. doi: 10.3109/00365529209096026.

DOI:10.3109/00365529209096026
PMID:1298047
Abstract

The radioimmunologic determination of cholecystokinin (CCK) has proved to be notoriously difficult. This is due to the specificity of antibodies, preparation of radiolabeled CCK and low CCK concentrations in human plasma. About 10 years ago we succeeded in developing two highly sensitive region-specific radioimmunoassays for CCK. Antibody T204 binds to the sulfated tyrosine region of CCK, while antibody 1703 reacts with biologically active molecular forms of CCK containing at least 14 amino acid residues. Both antibodies are devoid of significant cross-reaction with gastrin. By means of these two radio-immunoassays CCK concentrations were measured in both tissue and plasma of various species, including man. In addition, the molecular forms of CCK in tissue and plasma were characterized. These CCK assays were used to study the mechanism of CCK secretion. It appeared that digested rather than intact protein and fat stimulated CCK release from the small intestine. The physiologic and pathophysiologic role of CCK in humans was studied using CCK radioimmunoassays and specific CCK-receptor antagonists. CCK was found to play an important role in pancreatic enzyme secretion, gallbladder contraction, and gastrointestinal motility but possibly also in pancreatic carcinogenesis and regulation of satiety and satiation.

摘要

胆囊收缩素(CCK)的放射免疫测定已被证明极其困难。这是由于抗体的特异性、放射性标记CCK的制备以及人血浆中CCK浓度较低。大约10年前,我们成功开发了两种高度敏感的CCK区域特异性放射免疫测定法。抗体T204与CCK的硫酸化酪氨酸区域结合,而抗体1703与含有至少14个氨基酸残基的CCK生物活性分子形式发生反应。两种抗体与胃泌素均无明显交叉反应。通过这两种放射免疫测定法,测量了包括人类在内的各种物种的组织和血浆中的CCK浓度。此外,还对组织和血浆中CCK的分子形式进行了表征。这些CCK测定法用于研究CCK的分泌机制。结果表明,消化后的而非完整的蛋白质和脂肪刺激小肠释放CCK。使用CCK放射免疫测定法和特异性CCK受体拮抗剂研究了CCK在人类中的生理和病理生理作用。发现CCK在胰腺酶分泌、胆囊收缩和胃肠动力中起重要作用,但也可能在胰腺癌发生以及饱腹感和饱足感的调节中起作用。

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