Chow B K
Department of Zoology, University of Hong Kong.
Biochem Biophys Res Commun. 1995 Jul 6;212(1):204-11. doi: 10.1006/bbrc.1995.1957.
Secretin is a gastrointestinal hormone responsible for the regulation of bicarbonate, potassium ion and enzyme secretion from the pancreas. A cDNA encoding the human secretin receptor was isolated from a human pancreatic adenocarcinoma cell-line cDNA library using polymerase chain reaction and library screening techniques. The cDNA isolated is 1717 bp in length encoding a 440 amino acid long polypeptide. Computer analysis of the receptor indicated that it is a member of the glucagon-VIP-secretin receptor family and is a G-protein coupled receptor containing seven hydrophobic transmembrane domains. The receptor was subsequently expressed in COS-7 cells and was able to bind specifically to human secretin with high affinity as indicated by the competitive displacement assay. The human secretin receptor was found to be functionally coupled to the stimulation of adenylyl cyclase resulting in the accumulation of intracellular cAMP in a dose-dependent manner. By Northern blot analysis, a 1.8 Kb mRNA was detected in human pancreas and intestine, while weak hybridization signals were detected in human colon, kidney and lung. Functional characterization of this receptor should enhance our understanding of the physiology and pathophysiology of human secretin, its structure-function, receptor interaction and receptor tissue distribution.
促胰液素是一种胃肠激素，负责调节胰腺中碳酸氢盐、钾离子和酶的分泌。利用聚合酶链反应和文库筛选技术，从人胰腺腺癌细胞系cDNA文库中分离出编码人促胰液素受体的cDNA。分离出的cDNA长度为1717bp，编码一个440个氨基酸长的多肽。对该受体的计算机分析表明，它是胰高血糖素-VIP-促胰液素受体家族的成员，是一种含有七个疏水跨膜结构域的G蛋白偶联受体。随后，该受体在COS-7细胞中表达，竞争性置换试验表明它能够以高亲和力特异性结合人促胰液素。发现人促胰液素受体在功能上与腺苷酸环化酶的刺激偶联，导致细胞内cAMP以剂量依赖的方式积累。通过Northern印迹分析，在人胰腺和肠道中检测到1.8Kb的mRNA，而在人结肠、肾脏和肺中检测到微弱的杂交信号。对该受体的功能特性进行表征应能增强我们对人促胰液素的生理学和病理生理学、其结构功能、受体相互作用和受体组织分布的理解。
