STRESS-ACTIVATED PROTEIN-KINASE ACTIVATION IS THE EARLIEST DIRECT CORRELATE TO THE INDUCTION OF SECRETAGOGUE-INDUCED PANCREATITIS IN RATS

We compared the cellular events induced by hyperstimulation of rats wi th caerulein which induces acute pancreatitis, to bombesin, which does not induce pancreatitis. Both secretogogues induced the intracellular activation of trypsinogen and the colocalization of lysosomal hydrola ses and zymogen granules within 10-15 minutes. These data indicate tha t these parameters, previously thought to be crucial initiating events of pancreatitis, are not definitive cellular markers of the disease. We then compared the abilities of the two secretagogues to activate st ress-activated protein kinase (SAPK). Significant effects of caerulein hyperstimulation on SAPK activity were observed within 5 minutes, the maximum (57-fold) activation was evident after 15 minutes, and levels remained above control for at least 3 hours. In comparison, hyperstim ulation with bombesin induced a maximal 5-fold increase of SAPK activi ty which returned to basal within one hour. These data indicate that S APK activity is the earliest and best correlated cellular marker assoc iated with secretagogue-induced pancreatitis. (C) 1996 academic press, Inc.