Exocrine pancreas; molecular basis for intracellular signaling, damage and protection--Polish experience.

Polish experience in molecular pancreatology mostly involves experimental work on intracellular signal transduction mechanisms in pancreatic acinar cells. It was found that stimulation with cholecystokinin (CCK) or exposure of pancreatic acini to reactive oxygen species induces three separate signaling cascades leading to activation of ERKs, JNK/SAPKs and p38 MAPK. In pancreatic acini, ERK cascade is also activated by epidermal growth factor (EGF). However, CCK and EGF activate this cascade by different mechanisms. EGF activates the cascade in a classical Ras-dependent manner, while CCK-induced activation of the ERK cascade is Ras-independent. Furthermore, stimulation with CCK leads to a rapid activation of PKC, which in turn may directly activate Raf family of kinases. Freshly isolated pancreatic acini contain pancreatic stellate cells which respond to EGF by activation of ERK cascade. It is possible that stimulation with CCK and EGF induces a cross-talk between acinar and stellate cells. Isolated pancreatic acinar cells irradiated with UV-B die predominantly by apoptosis while necrosis predominates among the cells subjected to supraphysiological concentrations of CCK. In pancreatic acini subjected to stressful stimuli the regulation of apoptosis may involve interaction between ERK and p38 MAPK signaling pathways. Acute pancreatitis in rats and in humans is associated with a marked increase in the plasma level of leptin which is caused by increased production of this peptide in the inflamed pancreas. It is possible that exogenous leptin protects the pancreas against development of acute pancreatitis by the activation of nitric oxide pathway.