Pauwels S, Desmond H, Dimaline R, Dockray G J
J Clin Invest. 1986 Feb;77(2):376-81. doi: 10.1172/JCI112315.
Recent studies on the gene sequence encoding the human pyloric antral hormone, gastrin, indicate a precursor of 101 residues. We have now raised antibodies to a synthetic analogue corresponding to (Tyr)-human progastrin COOH-terminal pentapeptide. The antibodies could be used in radioimmunoassay to measure this peptide, but they did not react with corresponding fragments of procholecystokinin, porcine progastrin, or other human progastrin-derived peptides, notably heptadecapeptide gastrin (G17), and 34-residue gastrin (G34). Radioimmunoassay of human antral and duodenal extracts revealed a major peak of activity that corresponded to the native COOH-terminal fragment of progastrin, and occurred in approximately equimolar amounts with COOH-terminal G17 immunoreactivity. In addition, there was a minor peak of apparently higher molecular weight material. In some gastrinomas the latter material was the predominant immunoreactive form, and it occurred in higher molar concentrations than any other form of gastrin. Digestion of this material with trypsin liberated peptides that reacted with antibodies specific for the NH2-terminus of G34, and G17. On this basis the high molecular weight component was identified as a form of gastrin that extended from the COOH-terminus of the precursor to a point at least beyond the NH2-terminus of G34, and probably included the entire progastrin sequence. The results suggest differences in posttranslational processing pathways of progastrin in antrum, duodenum, and gastrinomas. They also indicate that the present experimental approach allows the identification of progastrin-like substances, which should open the way to studying the mechanisms of gastrin biosynthesis.
近期对编码人幽门窦激素胃泌素的基因序列研究表明，其前体由101个氨基酸残基组成。我们现已制备了针对一种合成类似物的抗体，该类似物对应于（酪氨酸）-人胃泌素原COOH末端五肽。这些抗体可用于放射免疫测定以检测该肽，但它们不与缩胆囊素原、猪胃泌素原或其他人胃泌素衍生肽的相应片段发生反应，尤其是十七肽胃泌素（G17）和34肽胃泌素（G34）。对人胃窦和十二指肠提取物的放射免疫测定显示，有一个主要的活性峰，它对应于胃泌素原的天然COOH末端片段，且与COOH末端G17免疫反应性的量大致相等。此外，还有一个分子量明显较高的物质的小峰。在一些胃泌素瘤中，后一种物质是主要的免疫反应形式，且其摩尔浓度高于任何其他形式的胃泌素。用胰蛋白酶消化该物质可释放出与针对G34和G17 NH2末端特异性抗体发生反应的肽。基于此，高分子量成分被鉴定为一种胃泌素形式，它从前体的COOH末端延伸至至少超过G34的NH2末端的一点，可能包括整个胃泌素原序列。结果表明胃窦、十二指肠和胃泌素瘤中胃泌素原的翻译后加工途径存在差异。它们还表明，目前的实验方法能够鉴定胃泌素原样物质，这应为研究胃泌素生物合成机制开辟道路。
