IMPAIRMENT OF INTRACELLULAR CALCIUM HOMEOSTASIS IN THE EXOCRINE PANCREAS AFTER CERULEIN-INDUCED ACUTE-PANCREATITIS IN THE RAT

1. We have measured intracellular calcium concentrations in basal cond itions and in response to cholecystokinin-octapeptide and acetylcholin e in pancreatic acini isolated from rats with caerulein-induced acute pancreatitis and compared them with those in control rats. 2. We also measured amylase secretion in basal conditions and in response to chol ecystokinin-octapeptide in both groups. 3. In pancreatic acini from ra ts with pancreatitis the basal intracellular calcium concentration was significantly increased (134.9+/-7.1 nmol/l compared with 71.8+/-2.9 nmol/l, P<0.001), Moreover, the maximum values of intracellular calciu m attained during the stimulation period were equivalent in acini from control and pancreatitic rats with no statistically significant diffe rences. 4. In acini from control rats the differences between the rest ing levels of intracellular calcium and the maximum intracellular calc ium values (Delta[Ca2+](i)) in response to several concentrations of c holecystokinin-octapeptide showed a clear dose-response relationship, with a half-maximal increase at 0.1 nmol/l and a maximal difference (D elta[Ca2+](i) = 259+/-50 nmol/l) at 1 nmol/l. In contrast, a right-shi fted response, with a statistically significant smaller increase, was observed in acini from pancreatitic rats. 5. Basal amylase release was significantly higher in acini from rats with pancreatitis (11.7+/-1.0 % of total compared with 5.9+/-1.1% of total, P<0.001). In contrast, c holecystokinin-octapeptide and acetylcholine-evoked amylase secretion was reduced by more than 85% in acini from pancreatitic rats. 6. In co nclusion, calcium homoeostasis in pancreatic acinar cells from rats wi th caerulein-induced pancreatitis seems to be impaired, These results suggest excessive release of acinar free ionized calcium, or damage to the integrity of mechanisms that restore low resting levels of intrac ellular free ionized calcium, and the consequent calcium toxicity coul d be the key trigger in caerulein-induced acute pancreatitis.