MODIFICATIONS IN CCKB RECEPTORS, MAPKINASE ACTIVITIES AND PARP ACTIVATION IN THREE MODELS OF INDUCED PANCREATITIS.

Abstract

Introduction: Pancreatitis results in partial destruction of the pancreatic gland through apoptosis and/or necrosis. In most pancreatitis models, regeneration of the gland occurs with time. In this study, our aim was to document the apoptosis phenomenon, the behavior of the CCKB receptor subtype and the timing of the regeneration processes following pancreatitis induction in the rat. Methods: Interstitial pancreatitis was induced either by cerulein in gelatin sc every 8h for 48h at 12μg kg−1(IP12) or by cerulein sc at 100μg kg−1 + 4 injection hourly at 50μg kg−1(IP100). Necrotizing pancreatitis resulted following a single i.p. arginine injection in water at 4.5g kg−1(AP). Rats were killed 1, 2 4, 8, 12, 16, 24 and 48h after the 1st injection. Pancreas were weighed, homogenized to measure poly ADP robose polymerase (PARP), an apoptosis marker, CCKB receptor proteins and perk as a regeneration marker. Results: Activated PARP was observed in the three models of induced pancreatitis. In the IP12 model, increases started at 8h to reach maximal values at 48h. In the IP100 model, increases started at 12h to peak at 48h whereas in the AP model, peak activations occurred at 16 and 48h. In IP12, CCKBR/NaKATPase ratios significantly decreased at 1h recovered control (C) values at 2, 4, 8, 12 and 16h to be reduced again at 24 and 48h. In IP100, ratios were increased at 1h, decreased at 2h, C values at 4h, reached maximal values at 8h and were significantly decreased at 16, 24 and 48h. In AP, ratios were significantly decreased at 1, 4 and 48h but remained at C values at 2, 8, 12, 16 and 24h. With regards to perk/MAPK ratios, higher values were observed at 2h in IP12 and at 4h in IP100. In AP, significant increases were observed at 4, 12 and 16h with a significant decrease at 48h. Conclusions: The three models of pancreatitis exhibited activation of apoptotic processes at different time periods. The CCKB receptors protein expression was generally repressed in the course of pancreatitis development in the three models. Bursts of regeneration as established by ERK phosphorylation were also observed in the three models with a more sustained activation in the AP group. Supported by NSERC Canada.