Povoski S P, Zhou W, Longnecker D S, Jensen R T, Mantey S A, Bell R H
Department of Surgery, University of Cincinnati College of Medicine, Ohio.
Gastroenterology. 1994 Oct;107(4):1135-46. doi: 10.1016/0016-5085(94)90239-9.
BACKGROUND/AIMS: Cholecystokinin (CCK) and gastrin stimulate growth of rodent pancreas in vivo. However, it remains unclear whether these growth effects are mediated specifically by CCK-A receptors, CCK-B receptors, or both. To clarify this issue, the present study examined the effect of highly selective and biologically active CCK agonists on pancreatic growth.
Rats were subcutaneously injected with either (1) CCK-8, a nonselective CCK agonist (2.50 micrograms/kg body wt); (2) A-71623, a selective CCK-A agonist, tert-butyl-oxycarbonyl-Trp-Lys (epsilon-N-2-methylphenylaminocarbonyl)-Asp-(N-methyl)-Phe-NH2 (1.84 micrograms/kg body wt); (3) SNF-8815; a selective CCK-B agonist, [(2R,3S)-beta-MePhe28, N-MeNle31]CCK26-33 (2.40 micrograms/kg body wt); or (4) saline (control) for 21 days. Rats were killed, and pancreatic weight, protein content, RNA content, DNA content, protein-DNA ratio, RNA-DNA ratio, pancreatic area per nucleus, and number of mitoses per 10,000 acinar cells were determined.
Nonselective CCK agonist significantly increased pancreatic weight, protein, RNA, and DNA contents, and number of mitoses per 10,000 acinar cells. Likewise, selective CCK-A agonist significantly increased pancreatic weight, protein, RNA, and DNA contents, protein-DNA ratio, RNA-DNA ratio, pancreatic area per nucleus, and number of mitoses per 10,000 acinar cells. In contrast, selective and biologically active CCK-B agonist had no effect.
These findings indicate that pancreatic growth is mediated specifically by CCK-A receptors in the rat in vivo.
背景/目的：胆囊收缩素（CCK）和胃泌素可刺激啮齿动物胰腺在体内生长。然而，这些生长效应是否由CCK-A受体、CCK-B受体或两者特异性介导仍不清楚。为阐明这一问题，本研究检测了高选择性和生物活性的CCK激动剂对胰腺生长的影响。
给大鼠皮下注射以下物质之一，持续21天：（1）CCK-8，一种非选择性CCK激动剂（2.50微克/千克体重）；（2）A-71623，一种选择性CCK-A激动剂，叔丁氧羰基-色氨酸-赖氨酸（ε-N-2-甲基苯基氨基羰基）-天冬氨酸-（N-甲基）-苯丙氨酸-酰胺（1.84微克/千克体重）；（3）SNF-8815，一种选择性CCK-B激动剂，[(2R,3S)-β-甲基苯丙氨酸28，N-甲基异亮氨酸31]CCK26-33（2.40微克/千克体重）；或（4）生理盐水（对照）。处死大鼠后，测定胰腺重量、蛋白质含量、RNA含量、DNA含量、蛋白质-DNA比值、RNA-DNA比值、每核胰腺面积以及每10000个腺泡细胞的有丝分裂数。
非选择性CCK激动剂显著增加了胰腺重量、蛋白质、RNA和DNA含量，以及每10000个腺泡细胞的有丝分裂数。同样，选择性CCK-A激动剂显著增加了胰腺重量、蛋白质、RNA和DNA含量、蛋白质-DNA比值、RNA-DNA比值、每核胰腺面积以及每10000个腺泡细胞的有丝分裂数。相比之下，选择性和生物活性的CCK-B激动剂没有作用。
这些发现表明，在大鼠体内，胰腺生长是由CCK-A受体特异性介导的。
