Graziano M P, Hey P J, Borkowski D, Chicchi G G, Strader C D
Department of Molecular Pharmacology and Biochemistry, Merck Research Laboratories, Rahway, NJ 07065.
Biochem Biophys Res Commun. 1993 Oct 15;196(1):141-6. doi: 10.1006/bbrc.1993.2226.
A human glucagon-like 1 peptide receptor has been cloned from the gastric tumor cell line HGT-1. The cDNA clone encodes a protein of 463 amino acids and is a member of the superfamily of seven transmembrane domain G protein coupled receptors. Transfection of the human GLP-1 receptor into COS-7 cells confers upon them high affinity binding for [125I] GLP-1 (7-36) amide. In membranes prepared from COS-7 cells transfected with the human GLP-1 receptor, the binding of [125I] GLP-1 (7-36) amide is inhibited with the rank order of potency GLP-1 (7-36) amide > glucagon > secretin, characteristic of a GLP-1 receptor. The human GLP-1 receptor is functionally coupled to increases in intracellular cAMP in these cells: incubation of COS-7 cells expressing the human GLP-1 receptor with GLP-1 (7-36) amide gives rise to a 4-fold increase in cyclic AMP over basal levels, with an EC50 of 25pM. Glucagon is also a full agonist but is 200-fold less potent than GLP-1 (7-36) amide in stimulating the human GLP-1 receptor.
已从胃肿瘤细胞系HGT-1中克隆出人类胰高血糖素样肽-1受体。该cDNA克隆编码一个由463个氨基酸组成的蛋白质，属于七跨膜结构域G蛋白偶联受体超家族。将人类GLP-1受体转染到COS-7细胞中，使其对[125I]GLP-1（7-36）酰胺具有高亲和力结合。在用人类GLP-1受体转染的COS-7细胞制备的膜中，[125I]GLP-1（7-36）酰胺的结合被抑制，其效力顺序为GLP-1（7-36）酰胺＞胰高血糖素＞促胰液素，这是GLP-1受体的特征。人类GLP-1受体在功能上与这些细胞内cAMP的增加相关联：用GLP-1（7-36）酰胺孵育表达人类GLP-1受体的COS-7细胞，会导致环磷酸腺苷比基础水平增加4倍，EC50为25pM。胰高血糖素也是一种完全激动剂，但在刺激人类GLP-1受体方面的效力比GLP-1（7-36）酰胺低200倍。
