STIMULATION OF IN-VIVO PANCREATIC GROWTH IN THE RAT IS MEDIATED SPECIFICALLY BY WAY OF CHOLECYSTOKININ-A RECEPTORS

Background/Aims: Cholecystokinin (CCK) and gastrin stimulate growth of rodent pancreas in vivo. However, it remains unclear whether these gr owth effects are mediated specifically by CCK-A receptors, CCK-B recep tors, or both. To clarify this issue, the present study examined the e ffect of highly selective and biologically active CCK agonists on panc reatic growth. Methods: Rats were subcutaneously injected with either (1) CCK-8, a nonselective CCK agonist (2.50 mu g/kg body wt); (2) A-71 623, a selective CCK-A agonist, -methylphenylaminocarbonyl)-Asp-(N-met hyl)-Phe-NH2 (1.84 mu g/kg body wt); (3) SNF-8815; a selective CCK-B a gonist, [(2R,3S)-beta-MePhe(28), N-MeNle(31)]CCK26-33 (2.40 mu g/kg bo dy wt); or (4) saline (control) for 21 days. Rats were killed, and pan creatic weight, protein content, RNA content, DNA content, protein-DNA ratio, RNA-DNA ratio, pancreatic area per nucleus, and number of mito ses 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, pr otein, RNA, and DNA contents, protein-DNA ratio, RNA-DNA ratio, pancre atic area per nucleus, and number of mitoses per 10,000 acinar cells. In contrast, selective and biologically active CCK-B agonist had no ef fect. Conclusion: These findings indicate that pancreatic growth is me diated specifically by CCK-A receptors in the rat in vivo.