Cholecystokinin-1 receptor protein up-regulation during pancreatic regeneration after acute haemorrhagic pancreatitis in rats

Abstract

Background: Cholecystokinin (CCK) plays an important role in regeneration after acute pancreatitis in rats. The present study was aimed to elucidate the role of CCK-1 receptor (CCK-1R) in acute pancreatitis. We investigated the serial changes in CCK-1R mRNA and protein levels and their immunolocalization after acute haemorrhagic pancreatitis induced in male Wistar rats by retrograde intraductal infusion of 4% sodium taurocholate (100 micro L 100 g(-1) body weight).

Methods: Histological changes were evaluated by haematoxylin and eosin staining. Pancreatic CCK-1R mRNA was determined by Northern blot analysis. Pancreatic CCK-1R protein was evaluated by immunoblot analysis and immunohistochemistry with a polyclonal antibody against rat CCK-1R protein.

Results: Histological findings revealed that newly formed acinar cells were detected at the periphery of tubular complexes on day 14, and normal architecture of lobules was observed focally on day 21. Pancreatic CCK-1R mRNA peaked on day 3 and thereafter gradually decreased. Cholecystokinin-1R protein rapidly increased after induction of pancreatitits, reaching a maximal level on day 3. On day 3, intense immunoreactivity for CCK-1R protein was observed in both the cytoplasm of vacuolized acinar cells and the tubular complexes. In the regenerative process after acute haemorrhagic pancreatitis in rats, the expression of pancreatic CCK-1R mRNA and protein increased, and intense immunoreactivity for CCK-1R protein was observed in tubular complexes in the cytoplasm of regenerated acinar cells.

Conclusion: These results suggest that CCK-1R contributes to pancreatic regeneration after acute haemorrhagic pancreatitis and that tubular complexes are involved in the process of acinar cell regeneration following pancreatic injury.