JUN KINASES ARE RAPIDLY ACTIVATED BY CHOLECYSTOKININ IN RAT PANCREAS BOTH IN-VITRO AND IN-VIVO

Stimulation of pancreatic acini from male Sprague-Dawley rats by both cholecystokinin (CCK)-8 and anisomycin caused an increase in p46(ink) and p55(ink) activities. Both forms of c-Jun amino-terminal kinase (JN K) were slightly activated at 5 min, reached a maximum at 30 min, and remained significantly increased at 60 min of CCK stimulation. By cont rast, p42(mapk) was activated fully by 5 min. In pancreatic acini stim ulated with different concentrations of CCK for 30 min, the minimal an d maximal JNK responses were observed at 30 pM and 100 nM CCK, respect ively; p42(mapk) activation was, as previously reported, much more sen sitive, with maximal activation by 1 nM CCK. Carbachol and bombesin al so stimulated JNK activity, while vasoactive intestinal peptide did no t. Neither activating protein kinase C nor increasing intracellular Ca 2+ significantly activated JNK. In in vivo experiments, rats were infu sed intravenously for 5 and 15 min with a secretory (0.1 mu g/kg/h) or supramaximal (10 mu g/kg/h) dose of the CCK analog cae rulein (CER). Secretory doses of CER induced a 4-fold increase of both forms of JNK in pancreatic tissue at 5 and 15 min, while at the same time points, s upramaximal stimulation with CER caused 4- and 27-fold increases, resp ectively, of these kinase activities. The secretory dose of CER slight ly increased the activities of both forms of mitogen-activated protein kinase, while the supramaximal dose induced a 10-fold increase of p42 (mapk) at 5 min. In conclusion, JNKs and mitogen-activated protein kin ases are rapidly activated in rat pancreatic acini stimulated with CCK as well as in pancreatic tissue during in vivo stimulation with CER. The large response to supramaximal CER stimulation may be of importanc e in the early pathogenesis of acute pancreatitis.