Alterations of Pancreatic Growth and of GP-2 Content in the Reserpinized Rat Model of Cystic Fibrosis

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Abstract
The chronically reserpinized rat is an experimental model for cystic fibrosis. In this study, we report the effects of two doses of reserpine (0.5 and 1.0 mg · kg-1 ·d-1) on the growth of the pancreas and on its content of the glycoprotein GP-2, a characteristic protein of the zymogen granule. An assessment of the effects of secondary malnutrition induced by the drug was also performed by adding a group of pair-fed animals. During the 7 d of treatment, body wt and food intake were monitored. These two parameters were significantly affected from the 4th d on. Pancreatic wt, DNA, protein, and activity of amylase and chymotrypsinogen were measured after 4 and 7 d of treatment; lipase activity and GP-2 content, after 7 d. Although the DNA content never did change, total protein diminished by 27% at the higher dose of reserpine. Pancreatic wt, amylase activity and GP-2 content were reduced by the treatment, while chymotrypsinogen and lipase activities were increased. Effects on pancreatic wt, amylase, chymotrypsinogen, and GP-2 were dose-dependent. Malnutrition had effects similar to reserpine on body wt, protein, amylase, and chymotrypsinogen. Pancreatic wt, lipase, and GP-2, however, were specifically altered by the chronic reserpine treatment. It is concluded from these results that reserpine induces, in the pancreas, specific alterations that are distinguishable from the accompanying malnutrition. These findings support the use of pancreatic wt, lipase, and GP-2 as specific markers of the effects of the drug on the pancreatic tissue in the chronically reserpinized rat model for cystic fibrosis. This is the first report of a modulation of GP-2 content induced by any treatment. It suggests that GP-2 is directly affected in the pancreas of the chronically reserpinized rat.