Relationship between carbachol hyperstimulation-induced pancreatic intracelluar trypsinogen and NF-κB activation in rats in vitro

Abstract

The relationship between intracelluar trypsinogen activation and NF-κB activation in rat pancreatic acinar cells induced by M3 cholinergic receptor agonist (carbachol) hyperstimulation was studied. Rat pancreatic acinar cells were isolated, cultured and treated with carbachol, the active protease inhibitor (pefabloc) and NF-κB inhibitor (PDTC) in vitro. Intracelluar trypsin activity was measured by using a fluorogenic substrate. The activity of NF-κB was monitored by using electrophoretic mobility shift assay. The results showed that after pretreatment with 2 mmol/L pefabloc, the activities of trypsin and NF-κB in pancreatic acinar cells treated with high concertrations of carbachol (10⁻³ mol/L) in vitro was significantly decreased as compared with control group (P<0.01). The addition of 10⁻² mol/L PDTC resulted in a significant decrease of NF-κB activities in pancreatic acinar cells after treated with high concertrations of carbachol (10⁻³ mol/L) in vitro, but the intracelluar trypsinogen activity was not obviously inhibited (P>0.05). It was concluded that intracelluar trypsinogen activation is likely involved in the regulation of high concertrations of carbachol-induced NF-κB activation in pancreatic acinar cells in vitro. NF-κB activation is likely not necessary for high concertrations of carbachol-induced trypsinogen activation in pancreatic acinar cells in vitro.

Keywords

pancreatic acinar cell / trypsinogen activation / NF-κB activation