ROLE OF CHOLECYSTOKININ-A (CCK-A) RECEPTOR IN PANCREATIC REGENERATIONAFTER PANCREATIC DUCT OCCLUSION - A STUDY IN RATS LACKING CCK-A RECEPTOR GENE-EXPRESSION

We examined the role of the cholecystokinin-A (CCK-A) receptor in acut e inflammatory and regenerative stages of experimental pancreatitis us ing a rat model lacking the CCK-A receptor [Otsuka Long-Evans Tokushim a Fatty (OLETF) rats]. OLETF and control [Long-Evans Tokushima Otsuka (LETO)] rats were prepared with an internal bile fistula and with obst ruction of pancreatic flow and were sacrificed 1-14 days later. Histol ogical examination was performed, and changes in pancreatic wet weight , protein concentration, CCK-A and -B receptor mRNA levels, tyrosine k inase activities, and plasma amylase and CCK levels were determined. T he plasma amylase level showed a transient increase on day 1, the CCK level remained at high levels throughout, and tyrosine kinase activity was increased significantly on day 3 but declined thereafter. These p arameters were comparable for both strains during the acute inflammato ry stage. However, no regenerative findings were observed by histologi cal examination and the protein concentration in the pancreas was sign ificantly lower in OLETF rats on days 7-14, during which time regenera tion was completed in LETO rats. These observations indicate that the absence of the CCK-A receptor did not modify the acute phase of pancre atitis but significantly retarded regeneration of the pancreatic tissu e.