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. METHODS: 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. RESULTS: 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. CONCLUSION: These findings indicate that pancreatic growth is mediated specifically by CCK-A receptors in the rat in vivo.
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. METHODS: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. RESULTS: 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. CONCLUSION: These findings indicate that pancreatic growth is mediated specifically by CCK-A receptors in the rat in vivo.
Authors: P Cordelier; J P Estève; C Bousquet; N Delesque; A M O'Carroll; A V Schally; N Vaysse; C Susini; L Buscail Journal: Proc Natl Acad Sci U S A Date: 1997-08-19 Impact factor: 11.205