DOSE-DEPENDENT PANCREATOTROPHIC EFFECT OF CHOLECYSTOKININ-OCTAPEPTIDE IN THE RAT: THE INFLUENCE OF STARVATION

• Published in: Pharmacological research 1998-04, Vol.37 (4), p.309-319
• Main Authors: NAGY, ISTVÁN, LÁSZIK, ZOLTÁN, MOHÁCSI, GÁBOR
• Format: Article
• Language: English
• Subjects: Animals; Body Water - metabolism; cholecystokinin-octapeptide, pancreatic hypertrophy, pancreatitis, islets of Langerhans, trypsinogen, pancreatic secretory trypsin inhibitor; DNA - biosynthesis; Dose-Response Relationship, Drug; Male; Organ Size - drug effects; Pancreas - drug effects; Pancreas - metabolism; Pancreas - pathology; Pancreatitis - chemically induced; Pancreatitis - metabolism; Pancreatitis - pathology; Protein Biosynthesis; Rats; Rats, Wistar; Sincalide - pharmacology; Starvation - metabolism; Starvation - physiopathology
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1006/phrs.1998.0304

Cholecystokinin (CCK) and its analogues are known to exert trophic effects on the exocrine pancreas, whereas at high doses, they produce pancreatic injury. This study was carried out to study the effect of starvation on the dose-dependent pancreatotrophic effect of CCK-8 in rats. Normal or fasted rats were treated with CCK-8 doses ranging from 0.5 to 32 and 0.5 to 8 μg kg−1, respectively, twice daily for 5 days. Pancreatic size, protein, DNA, secretory enzyme and trypsin inhibitor (PSTI) contents as well as histology were examined. In normal rats, CCK-8 increased the pancreatic content of protein, amylase, serine proteases and PSTI with maximum values between doses of 2 and 16 μg kg−1. The dose of 32 μg kg−1, however, yielded less trophic responses. Given to fasted rats, CCK-8 increased the weight as well as protein and secretory enzyme contents of the pancreas with maximum values between doses of 1 and 4 μg kg−1. The first dose supramaximum for the trophic responses was as low as 8 μg kg−1. Histology revealed necroinflammatory damage (acinar cell vacuolization, focal cell necrosis) in the exocrine pancreas at supramaximum doses of CCK-8 in both groups. Cell necroses and vacuolization were less but present even at doses optimum for trophism and exhibited dependence on both the dose of CCK-8 and nutrition. In either the normal or fasted animals, the periinsular acini were relatively less affected by the toxic effects of CCK-8 than the teleinsular ones. The results indicate that starvation makes the exocrine pancreas more sensitive to necroinflammatory effects of CCK-8. The relative protection seen in periinsular acini suggests a modulatory influence of islet hormones on development of CCK-induced acinar cell injury.