Generation and Possible Significance of Trypsinogen Activation Peptides in Experimental Acute Pancreatitis in the Rat

Abstract

Trypsinogen activation peptides (TAP) were quantified by radio-immunoassay in blood, urine, and peritoneal exudate of rats with experimental pancreatitis. Forty-four animals were studied, comprising a control group and four different induction techniques (cerulein, cerulein plus either 2- or 10-min intraductal glycodeoxycholic acid [GDOC] infusion, and cerulein plus intra-ductal GDOC with enterokinase [EK]). Significantly higher TAP concentrations were found at 6 h (or at death) in plasma and ascites of all pancreatitis groups compared with controls. TAP quantitation in hourly urine samples demonstrated significantly higher concentrations from the third hour onward in the most severe groups and from the fourth hour onward in the cerulein-treated rats. All nonsurviving rats had a plasma TAP of >2.5 nM/L, whereas only 1 of 34 surviving animals had such a concentration (p <0.001). A significant step-wise increase in total TAP in ascites was found when comparing the cerulein group, the two GDOC groups, and the EK group (p <0.001). Chromatography of samples with a high TAP content demonstrated comigration with synthetic TAP. We conclude that free TAP are present in blood, urine, and peritoneal exudate of rats with experimental pancreatitis of different pathogenesis and that the amount of TAP may be indicative of the severity of the disease process.