グアニリンの分子構造、細胞学、生理学とその臨床応用

鸟苷酸的分子结构、细胞学、生理学及其临床应用

基本信息

批准号：
06044104
负责人：
HAYAKAWA Tetsuo
金额：
$ 7.74万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1996
项目状态：
已结题

项目摘要

Guanylin, isolated from rat small intestine, is a 15 amino acid residue peptide structurally related to the heat-stable enterotoxin (STa) of E.coli. In order to understand its function in health and disease states, we have synthesized guanylin and its precursor related peptides and tried to determine their structure and bindings to their receptors and to identify its producing cells and their tharget organs. Nuclear magnetic resonance spectroscopy revealed that guanylin with disulfids positions 4-12 and 7-15 exists as a mixture of two stable conformations with compact spiral structures. Its isomer with disulfides positions 4-15 and 7-12 showed a single conformation.Immunohistochemical studies in human and rat intestine using antiserum against proguanylin 1-15 indicated that proguanylin-like immunoreactivities were present in the intestinal endocrine cells which were also positive somatostatin but negative to serotonin, suggesting proguanyline may be cosecreted with somatostatin. Progua … More nyline positive cells were abundant in the pyrolic antrum and duodenum. Very few cells were observed in the colon. Both guanylin and STa displaced the binding of ^<125>I-labelled guanylin to crude membrane preparations of rat small intestine in a dose dependent manner with Kd values around 10^<-6> M.The disulfide isomer, on the other hand, bound poorly to the membrane preparations. Most of ^<125>I-guanylin was incorporated into the kidney following the intravenous injection in anesthetized rats. It bound to the luminal surface of proximal tubules. In the collecting ducts, ^<125>I-guanylin appeared to be excreted via chief cells. Guanylin decreased the cell height and increased the luminal space of the inner medullary collecting ducts, suggesting that guanylin has a diuretic action in the collecting ducts. In the small intestine guanylin stimulated mucus secretion from goblet cells in crypts but not in the villi. It appears that guanylin control both intestinal and renal fluid secretion as both paracrine and endocrine hormones. Less

从大鼠小肠中分离出的鸟苷是与E.Coli的热稳定肠毒素（STA）结构相关的15个氨基酸居住肽。为了了解其在健康和疾病状态中的功能，我们已经合成了鸟苷及其前体相关的肽，并试图确定其与受体的结构和结合，并确定其产生的细胞及其tharget器官。核磁共振光谱表明，具有二硫化物位置为4-12和7-15的鸟根作为两种稳定会议的混合物，具有紧凑的螺旋结构。它具有二硫化位置4-15和7-12的异构体显示了一次会议。对人和大鼠肠中使用抗蛋白基蛋白1-15进行的免疫组织化学研究表明，在肠内内分泌细胞中存在类似甘油基蛋白样的免疫反应性，这在肠内，这也是呈阳性的，但伴随着促进性促进蛋白蛋白蛋白，促进了促进蛋白蛋白蛋白，促进了促进性。 Progua…更多的NYLINE阳性细胞在硫酸脂肪酸和十二指肠中很丰富。在结肠中观察到的细胞很少。瓜尼尔蛋白和STA都以剂量依赖性的方式将 ^<125> i标记的鸟烯基与大鼠小肠对粗膜制剂的结合，其二硫化物异构体在二硫化物异构体附近，另一方面是二硫化物异构体，与膜制剂结合不佳。麻醉大鼠静脉注射后，大多数 ^<125> i-瓜烷蛋白被掺入肾脏中。它与近端小管的腔表面结合。在收集管道中， ^<125> i-甘糖蛋白似乎通过主要细胞超过了。鸟根增长了细胞的高度，并增加了内髓质收集管道的腔空间，这表明鸟根在收集管道中具有利尿作用。在小肠中，鸟苷蛋白在隐窝中刺激了杯状细胞的粘液分泌，但在绒毛中却没有刺激粘蛋白分泌。似乎鸟根控制肠道和肾脏液体分泌是旁分泌和内分泌激素。较少的