Alterations of pancreatic amylase secretion in the reserpinized rat model of cystic fibrosis

Summary

Reserpine treatment resulted in altered enzyme secretion from rat pancreatic acini in response to carbamylcholine and secretin(1,2). This study was undertaken: (1) To evaluate if the alterations caused by reserpine can be prevented by EGF and/or cerulein treatments; (2) To determine the time-course of secretion recovery after reserpine treatment; and (3) To establish if EGF and/or cerulein treatments can accelerate such a recovery after the reserpine treatment. Male Sprague-Dawley rats (250-265 g) were used in these experiments. In experiment I, rats divided into three groups received either reserpine (R) or the reserpine vehicle for the controls (C) and the pair-fed controls (PF) for 7 d. During treatment, PF and R rats were given SC, twice a day, saline, EGF (10 μg/kg), cerulein (1 μg/kg), or both at the same dose. C rats received saline in gelatin. In experiment II, rats were treated for 7 d with reserpine or the vehicle as described in experiment I, were allowed a 30-d recovery period and then were killed. In experiment III, C, PF, and R rats were treated for 7 d as described in experiment I; on the 8th d and for the next 6 d, reserpine rats received saline (reserpine-saline), cerulein, EGF, or both cerulein + EGF at the same dose as indicated in experiment I. C and PF rats received saline in gelatin. After sacrifice, acini were prepared, and amylase dose-response curves to carbamylcholine (Cch) and secretin were established. EGF, cerulein, or their combination given to R rats did not improve the desensitized secretory response to Cch. The secretory responses to secretin remained altered in PF and R rats even after the hormonal treatment. After 30 d of recovery, normal secretory responses to Cch and to secretin were found in the PF- and R-treated rats; this recovery was also observed as early as 6 d in PF and R rats, and it was impaired by the cerulein treatment. In conclusion, under the present regimen, EGF did not have any major impact on the recovery process or prevention of the alterations caused by malnutrition and reserpine. Cerulein was the most potent factor capable of promoting recovery or preventing alterations of total pancreatic amylase concentration in the reserpinized rat model; however, it failed to prevent desensitization of amylase release to Cch or decreases of acinar cells’ response to secretin. Finally, the CCK analog prevented recovery of the secretory responses to Cch and secretin observed in the absence of any treatment.