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PAR2 activation may protect the acinar cell by enhancing secretion, but may still leave you in pain
Two regulatory elements of the exocrine pancreas, one new and one old, may interact to regulate previously undescribed physiological and pathological responses of the pancreas. The new targets are protease-activated receptors (PARs); the old elements are the serine proteases trypsin and tryptase, which are the most potent agonists of these G-protein-coupled receptors.1 The PAR family of G-protein-coupled receptors exhibits a distinct activation mechanism. Limited cleavage of the extracellular domain of PARs by serine proteases uncovers a peptide on the N-terminus that interacts with another extracellular region to activate the receptor. PAR isoforms exhibit a distinct tissue distribution and are selectively activated by specific classes of proteases. For example, the PAR2 isoform that is found in the pancreas on epithelial cells and nerves is selectively activated by trypsin and tryptase. While the role of the PAR2 in health and disease is currently being elucidated, recent studies have suggested that it might participate in pancreatic responses.
Previous findings by Nguyen et al2 could be relevant to the effects of pancreatic PAR2 under physiological and pathological conditions. They showed that activation of the pancreatic ductal cell PAR2 by trypsin results in activation of electrolyte secretion. The enhanced chloride secretion was mediated by PAR2-dependent increases in cellular calcium. This study suggests that if activated trypsin was released from the pancreatic acinar cells (which might occur even with physiological stimulation), it could stimulate fluid and electrolyte secretion from small duct cells and help clear activated enzymes from the pancreatic duct. It could also function as a back-up mechanism should the major mechanism of ductal secretion, cystic fibrosis transmembrane conductance regulator, fail. This study found that PAR2 was localised to the basolateral membrane, and trypsin generated by …
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