Abstracts
2002 Digestive Disease Week

# 105317 Abstract ID: 105317 Effect of Proteinase Activated Receptor (PAR) Activation on Bicarbonate Secretion (BS) by Pancreatic Duct Cells
Demitri Merianos, Carlos Alvarez, Newark, NJ; East Orange, NJ

PAR-2, the trypsin receptor, is highly expressed in the pancreas, particularly in the ducts (PDs). Pancreatitis is thought to result from inappropriate activation of trypsinogen in the pancreas and has been characterized by low bicarbonate secretion. We hypothesized that trypsin reduces BS through PAR-2 and examined this in isolated PD cells. Methods: Main PDs were cultured as explants from fresh bovine pancreas for 48-96h . Bicarbonate secretion was determined by pH-stat technique in Ussing chambers (n= 6-10 / group) clamping the luminal pH at 7.4. Trypsin, soybean trypsin inhibitor (sbTi, 0.1mg/ml) and thrombin (PAR-1-specific, 2.5nM) were added to lumen. Electrical parameters, LDH levels and histology were followed for signs of epithelial injury. Data shown are BS (mean?SEM ) normalized to baseline secretion for individual explants. Comparisons between groups by ANOVA. Results: Increasing doses of trypsin caused abrupt decreases in BS (see figure, * : p<0.01 vs sbTI-treated). This effect was negated in the presence of sbTi while thrombin had no effect. LDH levels and electrical parameters were unchanged, suggesting no damage to the epithelium from exposure to trypsin; confirmed on H&E examination. Conclusions: Luminal trypsin, acting through activation of apical membrane PAR-2 receptors on PD cells, can inhibit PD BS secretion in vitro in a dose-dependent manner. Activation of PAR-2 by prematurely activated trypsin in pancreatic juice may explain the reduced BS in pancreatitis. Long acting PAR-2 agonists lacking enzymatic activity could have a therapeutic role in controlling pancreatic secretion.