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Respective roles of CCK-A and B receptors in the regulation of pancreatic secretion

CCK-A和B受体在胰腺分泌调节中的各自作用

基本信息

批准号：
10470145
负责人：
MIYASAKA Kyoko
金额：
$ 5.25万
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 Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470145/
关键词：
CCK CCK receptor CCK-A receptor CCK-B receptor pancreas gene gene expression bile 膵外分泌ノックアウトマウス

项目摘要

In humans, CCK has been known to stimulate pancreatic enzyme secretion via CCK-A receptors. Nevertheless, it was recently reported that gene expression of CCK-A receptor in the human pancreas could not be detected by Northen blot analysis. In the present study, we examined the mechanism of regulation of human pancreas by CCK and compared with those in mice and rats.Any dose of CCK could not stimulate amylase release from the human pancreatic dispersed acini, whereas GRP and acetylsholine did. The amylase release stimulated by acetylcholein and GRP were inhibited by atropine and a GRP antagonist, respectively. CCK-A receptor gene expression was not detected by Northern blot analysis but CCK-B receptor gene expression was detected in the human pancreas. Autoradiography using aィイD1125ィエD1-CCK-8 revealed positive binding sites in the human pancreas and these bindings were replaced by a CCK-B receptor antagonist but not by a CCK-A receptor antagonist. 1ィイD1125ィエD1-CCK-8 also bound human duo … More denum and was replaced by CCK-A receptor antagonist. Therefore, we confirmed that CCK-B receptors, not A receptors, were rich in human pancreas and that CCK did not stimulate amylase release from the acinar cells, directly.In rats, vagal afferent nerves in the stomach was responsible for CCK and the excitation was blocked by CCK-A receptor antagonist, not by B receptor antagonist. Taken together, it is interpreted that CCK stimulated human pancreas via vagal afferent nerve and passing through the vagal complex in the brain (vago-vagal reflex).The bile and pancreatic juice secretion were examined in CCD-B receptor gene knockout mice. The lack of CCK-B receptor did not modify these secretions, or pancreatic growth. Thus, CCK-B receptor is not mandatory for the bile and pancreatic secretion or other regulation may compensate CCK-B receptor function. The CCK-A receptor gene knockout mice have been generated. They shows normal growth and are fertile. The bile and pancreatic juice secretion were not stimulated by CCK but were responsible for other stimulants such as GRP and acetylcholine. The pancreatic wet weight was not different among three genotypes. In rats, CCK-A receptor gene expression has been known to appear after birth. We reported this gene expression was correlated with demthylation. Less

在人类中，已知CCK通过CCK-A受体刺激胰腺酶分泌。然而，最近有报道称，人胰腺中CCK-A受体的基因表达不能通过Northen印迹分析来检测。本研究探讨了CCK对人胰腺的调节机制，并与小鼠和大鼠的结果进行了比较，结果表明：任何剂量的CCK均不能刺激人胰腺分散腺泡的淀粉酶释放，而GRP和乙酰胆碱则能刺激人胰腺分散腺泡的淀粉酶释放。阿托品和GRP拮抗剂分别抑制乙酰胆碱和GRP刺激的淀粉酶释放。北方印迹分析未检测到胆囊收缩素A受体基因表达，但胆囊收缩素B受体基因在人胰腺中有表达。用胰蛋白酶D1125肽D1-CCK-8的放射自显影显示人胰腺中的阳性结合位点，这些结合被CCK-B受体拮抗剂取代，但不被CCK-A受体拮抗剂取代。1人D1125人D1-CCK-8也结合人duo ...更多信息用CCK-A受体拮抗剂替代。因此，我们证实人胰腺中含有丰富的CCK-B受体而非A受体，CCK不直接刺激腺泡细胞释放淀粉酶，大鼠胃内迷走传入神经参与CCK的兴奋，CCK-A受体拮抗剂可阻断CCK-B受体的兴奋，而B受体拮抗剂则不能阻断CCK-B受体的兴奋。结论CCK通过迷走神经传入神经刺激人胰腺，并通过脑内迷走神经复合体（迷走-迷走反射），刺激人胰腺分泌胆汁和胰液。CCK-B受体的缺乏没有改变这些分泌或胰腺生长。因此，CCK-B受体对胆汁和胰腺分泌不是强制性的，或者其他调节可以补偿CCK-B受体功能。建立了CCK-A受体基因敲除小鼠模型。它们生长正常，繁殖能力强。胆囊收缩素对胆汁和胰液分泌无刺激作用，但对其他刺激物如玻璃酸钠和乙酰胆碱有促进作用。胰腺湿重在3种基因型间无显著差异。在大鼠中，已知CCK-A受体基因表达在出生后出现。我们报道了该基因的表达与去甲基化相关。少