Carraway R E
J Biol Chem. 1984 Aug 25;259(16):10328-34.
Using a radioimmunoassay directed toward the COOH-terminal, biologically active region of mammalian neurotensin (NT), the rapid (within seconds) generation of immunoreactive NT (iNT) during acid extraction of mammalian and avian gastric tissues has been demonstrated. Levels of iNT were shown to increase 25-200-fold in time. The reaction occurred in 0.1 N HCl and 2 N acetic acid and was prevented by raising the pH above 5 or by adding acetone. The temperature and pH dependence and the ability of pepstatin A to inhibit the reaction suggested the involvement of a pepsin-related acid protease. Furthermore, the reaction could be mimicked by incubating a stabilized gastric extract with hog pepsin at pH 2. Size exclusion chromatography demonstrated the presence of a precursor-like substance with an apparent Mr of 60,000. Although iNT generated in avian and mammalian gastric extracts could be distinguished chromatographically from NT in that species, the partially purified gastric iNT was active in a bioassay for NT which quantitates changes in vascular permeability after intradermal injection into rats. One might suggest that iNT serves as a signal within the gastric lumen, being generated at low pH by secreted pepsin. It is also possible that iNT could be formed within blood or gastric interstitial fluid by the action of pepsin-related (cathepsin or renin-like) enzymes at normal physiologic pH.
利用针对哺乳动物神经降压素（NT）羧基末端生物活性区域的放射免疫分析法，已证实在对哺乳动物和鸟类胃组织进行酸提取过程中，免疫反应性NT（iNT）能迅速（数秒内）生成。结果显示iNT水平会随时间增加25至200倍。该反应在0.1N盐酸和2N乙酸中发生，通过将pH值提高到5以上或添加丙酮可阻止反应。温度和pH依赖性以及胃蛋白酶抑制剂A抑制该反应的能力表明，反应涉及一种与胃蛋白酶相关的酸性蛋白酶。此外，通过在pH值为2的条件下将稳定的胃提取物与猪胃蛋白酶一起孵育，可以模拟该反应。尺寸排阻色谱法表明存在一种表观分子量为60,000的前体样物质。尽管在鸟类和哺乳动物胃提取物中生成的iNT在色谱上可与该物种中的NT区分开来，但部分纯化的胃iNT在NT生物测定中具有活性，该测定通过皮内注射到大鼠体内后定量血管通透性变化来进行。有人可能会认为，iNT在胃腔内充当信号，由分泌的胃蛋白酶在低pH值下生成。也有可能iNT在正常生理pH值下由与胃蛋白酶相关的（组织蛋白酶或肾素样）酶在血液或胃间质液中形成。
