Cerulein-induced acute pancreatitis in rats: evidence for reduced calcium affinity of secretory granule membranes

Abstract

Membranes of secretory granules in pancreatic acinar cells seem to be interrelated in the regulation of intragranule Ca2+ concentrations. Since low intragranule Ca2+ levels are involved in zymogen stabilization versus autoactivation of proteases, a disturbance of the Ca2(+)-regulating system in secretory granules could be invoked to account for uncontrolled proenzyme activation. This is proposed as the initial mechanism in the pathogenesis of acute pancreatitis. Using pancreatic subcellular fractions obtained from control rats and after induction of acute cerulein pancreatitis we found a markedly reduced Ca2+ affinity of membranes from the secretory granule fraction in pancreatitis. The strong Ca2+ binding of control zymogen granule membranes primarily seemed to be a function of non-proteinacous membrane components, e.g. phosphatidylinositols. It is suggested, that part of the inner surface of membranes from secretory granules acts as a calcium-buffering system that works in synergy with other protective mechanisms to stabilize the zymogen granule population. In cerulein pancreatitis there seemed to be an imbalance of this system.