Kristian Agmund Haanes:
The role of purinergic signalling in exocrine pancreas

Date: 30-11-2012    Supervisor: Ivana Novak

ATP is a fundamentally important molecule in intracellular processes, especially recognised as the molecular source of energy. ATP is however also released as a signal from most cell types, and extracellular signalling by ATP goes under the common name purinergic signalling and it includes release mechanisms, receptors and breakdown enzymes. The work presented herein illustrates that ATP is present and is taken up into the zymogen granules of pancreatic acinar cells by the vesicular nucleotide transporter. Zymogen granules also contain the digestive enzymes in the acinar cells. Various stimuli release ATP, including a bile acid, CDC, which plays a role in pathophysiology of pancreatic diseases. This pathophysiological released ATP can act on surrounding cells, such as pancreatic stellate cells found around the acinar cells. We here show that ATP has a dual effect on pancreatic stellate cells. At low concentrations it stimulates proliferation, whereas it at higher concentrations is lethal to the cells, both caused by the purinergic P2X7 receptor.