Presence of pancreatitis-associated protein in pancreatic acinar cells of rats treated with chlorophenylalanine methyl ester.

The biological significance and function of pancreatitis-associated protein (PAP), identified in 1984 as a new secretory protein appearing during pancreatitis, remain to be elucidated. The purpose of this study was to evaluate the presence of PAP in pancreatic tissue upon its exposure to chlorophenylalanine methyl ester (CPME), a drug known to disrupt the regulated secretory pathway of acinar cells, an experimental condition that differs from acute pancreatitis. Pancreatic tissues were processed either for immunocytochemistry or for Northern blot analysis at 17-72 h after a single intraperitoneal injection of CPME in rats. Pancreatic acinar cells displayed endoplasmic reticulum intracisternal crystals consisting of an abnormal aggregation of secretory proteins as well as a sub-population of small and aberrant secretory granules. PAP mRNA was strongly increased at 17-24 h after CPME treatment, and PAP immunoreactivity was detected along the regulated secretory pathway, particularly in the small and aberrant secretory granules at these same time points. Levels of PAP and PAP mRNA decreased gradually, to become undetectable after 72 h. Autoradiographic experiments demonstrated that these small aberrant granules stored preferentially newly synthesized proteins. Our results indicate that the induction of PAP is not exclusive to acute pancreatitis since it appears in pancreatic cells as a response to certain insults and is secreted preferentially through a particular population of small aberrant granules.