Acute pancreatitis can be induced in the rat by high doses of cerulein, a cholecystokinin analogue. Regeneration of the pancreatic gland after this aggression can be accelerated by endogenous or exogenous cholecystokinin. However, the biochemical and molecular events associated with the cholecystokinin-induced regeneration process have not yet been identified. This study was therefore undertaken to determine the potential involvement of particulate and crude cytosolic tyrosine kinases as well as phospholipase D (PLD) in the course of pancreatitis induction and during regeneration. Acute pancreatitis was induced by cerulein, 12 micrograms kg-1, every 8 h for 2 days; this treatment was followed by 3 days of rest, and the regeneration treatment was started on the morning of the sixth day, with cerulein given at 1 microgram kg-1 every 8 h for 1-4 days. Animals were sacrificed 1, 3, 6, 12, 24, and 48 h after the first cerulein injection (high dose), on the morning of the sixth day (end of the rest period), and on the morning of the seventh and tenth days (low dose, regeneration period). After sacrifice, pancreata were excised and prepared for tyrosine kinase and PLD assays. Parallel increases in tyrosine kinase and PLD activities were observed from 6 to 48 h during pancreatitis induction and at the end of the resting period. Activities returned to control values during the regeneration period in the untreated cerulein-pancreatitis groups.(ABSTRACT TRUNCATED AT 250 WORDS)