Impairment of intracellular calcium homoeostasis in the exocrine pancreas after caerulein-induced acute pancreatitis in the rat.
1. We have measured intracellular calcium concentrations in basal conditions and in response to cholecystokinin-octapeptide and acetylcholine 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 cholecystokinin-octapeptide in both groups. 3. In pancreatic acini from rats 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 calcium attained during the stimulation period were equivalent in acini from control and pancreatitic rats with no statistically significant differences. 4. In acini from control rats the differences between the resting levels of intracellular calcium and the maximum intracellular calcium values (delta[Ca2+]i) in response to several concentrations of cholecystokinin-octapeptide showed a clear dose-response relationship, with a half-maximal increase at 0.1 nmol/l and a maximal difference (delta[Ca2+]i = 259 +/- 50 nmol/l) at 1 nmol/l. In contrast, a right-shifted 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, cholecystokinin-octapeptide and acetyl-choline-evoked amylase secretion was reduced by more than 85% in acini from pancreatitic rats. 6. In conclusion, calcium homoeostasis in pancreatic acinar cells from rats with 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 intracellular free ionized calcium, and the consequent calcium toxicity could be the key trigger in caerulein-induced acute pancreatitis.
Bragado
M J
MJ
Departamento de Fisiología y Farmacología, Universidad de Salamanca, Spain.
San Román
J I
JI
González
A
A
García
L J
LJ
López
M A
MA
Calvo
J J
JJ
D000109:Acetylcholine / Q000494:pharmacology; D000208:Acute Disease; D000681:Amylases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002108:Ceruletide; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis; D007424:Intracellular Fluid / Q000378:metabolism*; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010195:Pancreatitis / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012844:Sincalide / Q000494:pharmacology
D002108:Ceruletide; D000681:Amylases; D012844:Sincalide; D000109:Acetylcholine; D002118:Calcium