PLASMA-IMMUNOREACTIVE CATIONIC TRYPSIN(OGEN) PATTERN IN RESERPINIZED RAT MODEL OF CYSTIC-FIBROSIS - RESEMBLANCE TO HUMANS

Plasma immunoreactive cationic trypsin(ogen) is elevated in cystic fib rosis during early infancy, before exocrine pancreatic insufficiency i s fully developed. The recently developed cystic fibrosis mouse model carrying a mutated gene presents only minor pathologic findings in the pancreas. However, the reserpinized rat model shows cystic fibrosis-l ike defects in various exocrine glands, including the exocrine pancrea s. Plasma immunoreactive cationic trypsin(ogen) has not been studied y et in this model. The present study explored the plasma immunoreactive cationic trypsin(ogen) pattern and possible mechanisms in this rat mo del. Plasma immunoreactive cationic trypsin(ogen) (RIA), pancreatic ju ice volume, protein, and trypsin, and pancreas weight were determined in rats treated with reserpine (0.5 mg/kg/day subcutaneously) for four or seven days, following cerulein stimulation (5 mu g/kg/dose intrape ritoneally), versus pair-fed controls, The first of four consecutive 3 0 min periods revealed peak values in all parameters, Four-day reserpi ne-treated rats demonstrated significantly higher plasma immunoreactiv e cationic trypsin(ogen) levels (167.3 +/- 12.8 vs 88.9 +/- 6.1 ng/ml; P < 0.0001) with similar values of pancreatic juice trypsin (8.2 +/- 2.4 vs 6.6 +/- 1.8 units/mg protein; P = NS) and volume (5.6 +/- 1.3 v s 4.2 +/- 1.6 mg/min/g pancreas; P = NS), compared to controls, Rats t reated with reserpine for seven days revealed significantly lower valu es of plasma immunoreactive cationic trypsin(ogen) (39.2 +/- 8.4 vs 66 .8 +/- 4.9 ng/ml; P < 0.001), pancreatic juice trypsin (1.9 +/- 0.3 vs 3.2 +/- 0.9 units/mg protein; P < 0.001) and volume (1.6 +/- 0.7 vs 3 .1 +/- 0.6 mg/min/g pancreas; P < 0.001) compared to controls. We conc lude that the reserpinized rat model resembles human cystic fibrosis a s to elevated plasma immunoreactive cationic trypsin(ogen) before exoc rine pancreatic insufficiency is fully developed. Since exocrine pancr eatic volume secretion is intact at this stage, the mechanism of eleva ted plasma immunoreactive cationic trypsin is probably not due to duct ular obstruction. We suggest that this model be studied further in ord er to investigate other possible mechanisms.