| Pancreatic zymogen granules are specialized for enzyme storage and secretion. Purinergic signaling, through the ligand ATP, is proposed to be an important step in pancreatic physiology. The project objectives were to; (1) determine the zymogen granule content of ATP; (2) identify purinergic receptor subtypes expressed by rat acini; (3) determine the secretory response to purinergic manipulation; (4) measure the intracellular calcium response to receptor activation; and (5) identify signaling proteins that associate with the receptors. The results indicate that granules contain mM levels of ATP and that P2Y2, P2Y4 and P2X4 receptors are expressed. Further, purinergic agonists caused a significant increase in amylase release and intracellular calcium, while purinergic antagonists decreased both parameters. Finally, the results show that Erk2, PI3K and Akt kinases are recruited to the P2Y receptors following activation. This study demonstrates that ATP is an effective paracrine signal and offers a novel mechanism for pancreatic cellular regulation. |
