Intraduct enterokinase is lethal in rats with experimental bile-salt pancreatitis

Controlled intraduct infusion and peri-acinar dispersal of 100 microliter buffer containing sodium glycodeoxycholate (GDOC) at concentrations of 8.5, 17 and 34 mmol/l in rats caused a progressively severe acute pancreatitis from which none of the animals died over the experimental period. Infusion of affinity-purified active human enterokinase in buffer did not cause pancreatitis, presumably because of the inability of the macromolecule to gain access to its specific intracellular substrate trypsinogens. The addition of enterokinase 200 ng to GDOC 34 mmol/l in the infusate resulted in a severe systemic disturbance and a form of acute necrotizing pancreatitis which was uniformly and rapidly lethal. This effect was not seen when equimolar trypsin was substituted for enterokinase. These findings show that enterokinase specifically increases the lethality of experimental bile salt pancreatitis and suggest that this bile-borne enzyme may in some cases pose a significant clinical threat.