权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Isolation and Bioactivity of Putative Cholecystokinin-Releasing Reptide From rat Small Intenstinal Mucosa

大鼠小肠粘膜推定胆囊收缩素释放肽的分离和生物活性

基本信息

批准号：
02670332
负责人：
MIYASAKA Kyoko
金额：
$ 1.41万
依托单位：
Tokyo Metropolitan Institute of Gerontology
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670332/
关键词：
CCK-RP pancreatic secretion conscious rat bile CCK CCKーRP ネット放出ペプチド

项目摘要

Paiicreatic exocrine secretion in the conscious rat is regulated by proteases in the intestine secreted by the pancreas, and cholecystokinin (CCK) is known to be involved in the mechanism. We proposed that the release of CCK was regulated by a CCK-releasing factor secreted into the ifitestinal lumen from the proximal intestine. We isolated and partially purified a CCK-releasing factor from rat small intestine by gel filtration and high performance liquid chromatography. The partially purified CCK-releasing factor increased pancreatic exocrine secretions and plasma CCK concentrations in conscious rats and this activity was abolished after the incubation with trypsin. The bioactivity of the partially purified CCK-releasing factor was confirmed. The role of luminal bile salt (taurocholate) in regulation of rat pancreatic secretion was examined by studies on the effects of luminal stimulants on pancreas during infusion of various concentrations of taurocholate into the duodenum of conscious rats. Rats with external bile and pancreatic fistulac were used. 8-200 mM of taurocholate was infused at a rate of 1 ml/h instead of returning the bile. Pancreatic juice was collected for a 2-hour period and then 2 mug of pancreatic secretory trypsin inhibitor-61 (PSTI-61) (= monitor peptide) or partially purified putative CCK releasing peptide from rat intestine (intestinal CCK-RP) was injected into the duodenum (1 ml/min). Continuous infusion of taurocholate maintained a constant rate of pancreatic secretion, except at a concentration of 8 mM, which resulted in slight increase in pancreatic secretion. Both PSTI-61 and intestinal CCK-RP significantly increased pancreatic secretions during infusion of 20 or 40 mM taurocholate, but had no significant effect during, infusion of 80 or 200 mM taurocholate. Therefore, higher concentrations of taurocliolate in the intestine prevented the stimulatory effects of luminal stimulants, probably by preventing the latter from reaching CCK cells.

清醒大鼠胰腺外分泌受胰腺分泌的肠道蛋白酶调节，胆囊收缩素（CCK）参与了这一机制。我们认为CCK的释放受近端小肠分泌到肠腔的CCK释放因子的调节。采用凝胶过滤和高效液相色谱法从大鼠小肠中分离纯化了一种CCK释放因子。部分纯化的CCK-释放因子增加清醒大鼠胰腺外分泌和血浆CCK浓度，这种活性与胰蛋白酶孵育后被取消。部分纯化的CCK-释放因子的生物活性得到证实。通过向清醒大鼠十二指肠内注入不同浓度的牛磺胆酸盐（taurocholate），研究管腔刺激剂对胰腺的影响，探讨管腔胆汁盐（taurocholate）在调节大鼠胰腺分泌中的作用。采用胆胰外瘘大鼠模型。以1 ml/h的速率输注8-200 mM牛磺胆酸盐，而不是返回胆汁。收集胰液2小时，然后将2 μ g胰腺分泌性胰蛋白酶抑制剂-61（PSTI-61）（=监测肽）或部分纯化的假定的大鼠肠CCK释放肽（肠CCK-RP）注射到十二指肠（1 ml/min）。牛磺胆酸盐的连续输注保持恒定的胰腺分泌速率，除了在8 mM的浓度下，其导致胰腺分泌轻微增加。PSTI-61和肠CCK-RP显着增加胰腺分泌期间输注20或40 mM牛磺胆酸盐，但没有显着的效果，输注80或200 mM牛磺胆酸盐。因此，在肠道中较高浓度的牛磺克利酯阻止了管腔刺激剂的刺激作用，可能是通过阻止后者到达CCK细胞。