ONE-YEAR TREATMENT WITH CHOLECYSTOKININ-OCTAPEPTIDE AND SECRETIN - EFFECTS ON PANCREATIC TROPHISM IN THE RAT

The effects of long-term, administration of cholecystokinin octapeptid e (CCK-8) with or without secretin on the pancreas were examined in gr oups of rats treated with: (1) CCK-8 (1 mu g kg(-1)); (2) secretin + C CK-8 (1 mu g kg(-1) of each); or (3) saline, administered subcutaneous ly twice daily for 5 out of 7 days for 6 or 12 months. A number of rat s from all groups were studied for: (1) pancreatic size and biochemica l composition (n = 6 for each group); (2) pancreatic secretion in the anesthetized state (n = 5 for each group); and (3) pancreatic histolog y (n = 6 for each group) after a 6-month treatment period. The rest of the animals treated for an additional 6-month period (n = 13 for each group) were examined for pancreatic size and histology. CCK-8 increas ed the weight of the pancreas and its contents of DNA, protein, trypsi nogen, chymotrypsinogen, proelastase, secretory trypsin inhibitor and amylase, but not that of lipase when given for 6 months, whereas admin istration of secretin + CCK-8 doubled the pancreatic content of lipase and increased all trophic parameters (except the amylase content) ove r those of CCK-8-treated rats. Maximum pancreatic volume and protein o utputs in response to CCK-8 were higher in both of the hormone-treated groups than in the control; the sensitivity to the secretory action o f CCK-8 was not-altered. Pancreatic mass increased in response to eith er treatment after 12 months as well. Histological examination did not reveal pancreatic neoplasia in either group. The results indicate tha t long-term administration of CCK-8 or secretin + CCK-8 in rats result s in sustained pancreatic hypertrophy and hyperplasia with secretory h yperfunction with no evidence of neoplastic alterations. (C) 1997 The Italian Pharmacological Society.