Takiguchi Soichi, Suzuki Shinji, Sato Yuko, Kanai Setsuko, Miyasaka Kyoko, Jimi Atsuo, Shinozaki Hirotsugu, Takata Yutaka, Funakoshi Akihiro, Kono Akira, Minowa Osamu, Kobayashi Tomoko, Noda Tetsuo
Division of Chemotherapy, National Kyushu Cancer Center, Minamiku Fukuoka, Japan.
Pancreas. 2002 Apr;24(3):276-83. doi: 10.1097/00006676-200204000-00011.
The cholecystokinin (CCK) family of peptides and receptors is present throughout the brain and gastrointestinal tract. The CCK receptors can be pharmacologically subdivided into two subtypes: CCK-A and CCK-B. CCK-A receptor is enriched in the pancreas of mice.
To determine pancreatic functions in a CCK-A receptor deficient mouse mutant generated by gene targeting in embryonic stem cells. The targeting vector contained lacZ and neo insertions in exon 2.
To examine exocrine functions, amylase release from the dispersed acini in vitro was examined. In the in vivo study, the mixture of bile-pancreatic juice was collected, and amylase, bicarbonate, and bile acid outputs were determined after the administration of various stimulants. The cystic duct of the gallbladder and the pylorus were ligated to exclude the involvement of gallbladder contraction and gastric acid. Pancreatic enzyme content was measured, and histologic examinations by HE and lacZ staining were conducted. To examine endocrine functions, oral glucose tolerance test (2 g/kg) was determined.
The body weight, pancreatic wet weight, and enzyme content in the pancreas were similar among the three genotypes. Amylase release in vivo and in vitro and bicarbonate secretion in vivo were not stimulated by CCK-8 in CCK-AR (-/-) mice, whereas the responses to other stimulants were substantial in (-/-) mice. Administration of secretin did not increase bicarbonate secretion regardless of genotype. A normal glucose tolerance was observed in (-/-) mice. Acinar cells, islets, and duct cells were stained by lacZ, and HE staining revealed no pathologic findings.
The CCK-A receptor is important for pancreatic exocrine secretion, but not essential for maintaining glucose concentration and pancreatic growth in mice.
胆囊收缩素（CCK）肽家族和受体存在于整个大脑和胃肠道中。CCK受体在药理学上可分为两种亚型：CCK-A和CCK-B。CCK-A受体在小鼠胰腺中含量丰富。
确定通过胚胎干细胞基因靶向产生的CCK-A受体缺陷小鼠突变体的胰腺功能。靶向载体在外显子2中包含lacZ和neo插入片段。
为了检查外分泌功能，检测了体外分散腺泡中淀粉酶的释放。在体内研究中，收集胆汁-胰液混合物，并在给予各种刺激物后测定淀粉酶、碳酸氢盐和胆汁酸的输出量。结扎胆囊的胆囊管和幽门以排除胆囊收缩和胃酸的影响。测量胰腺酶含量，并进行苏木精-伊红（HE）染色和lacZ染色的组织学检查。为了检查内分泌功能，测定了口服葡萄糖耐量试验（2 g/kg）。
三种基因型小鼠的体重、胰腺湿重和胰腺酶含量相似。CCK-AR（-/-）小鼠体内和体外的淀粉酶释放以及体内的碳酸氢盐分泌不受CCK-8刺激，而（-/-）小鼠对其他刺激物的反应显著。无论基因型如何，给予促胰液素均未增加碳酸氢盐分泌。（-/-）小鼠观察到正常的葡萄糖耐量。腺泡细胞、胰岛和导管细胞被lacZ染色，HE染色未发现病理结果。
CCK-A受体对小鼠胰腺外分泌很重要，但对维持小鼠血糖浓度和胰腺生长并非必需。
