Plasma immunoreactive cationic trypsin(ogen) pattern in reserpinized rat model of cystic fibrosis

Abstract

Plasma immunoreactive cationic trypsin (ogen) is elevated in cystic fibrosis during early infancy, before exocrine pancreatic insufficiency is 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-like defects in various exocrine glands, including the exocrine pancreas. Plasma immunoreactive cationic trypsin (ogen) has not been studied yet in this model. The present study explored the plasma immunoreactive cationic trypsin (ogen) pattern and possible mechanisms in this rat model. Plasma immunoreactive cationic trypsin (ogen) (RIA), pancreatic juice 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 micrograms/kg/dose intraperitoneally), versus pair-fed controls. The first of four consecutive 30 min periods revealed peak values in all parameters. Four-day reserpine-treated rats demonstrated significantly higher plasma immunoreactive 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 vs 4.2 +/- 1.6 mg/min/g pancreas; P = NS), compared to controls. Rats treated with reserpine for seven days revealed significantly lower values 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 conclude that the reserpinized rat model resembles human cystic fibrosis as to elevated plasma immunoreactive cationic trypsin (ogen) before exocrine pancreatic insufficiency is fully developed. Since exocrine pancreatic volume secretion is intact at this stage, the mechanism of elevated plasma immunoreactive cationic trypsin is probably not due to ductular obstruction. We suggest that this model be studied further in order to investigate other possible mechanisms.

Serum feline trypsin-like immunoreactivity following administration of ceruletide to healthy cats

“…14,15 Administration of secretin in combination with CCK-8 caused a significant doserelated increase in serum TLI in rats, 16 and in rats with experimentally induced pancreatic fibrosis, the change in plasma immunoreactive cationic TLI in response to cerulein administration depended on the degree of fibrosis. 17 Thus, measuring the change in serum fTLI in response to administration of a pancreatic stimulant may be useful in diagnosing chronic pancreatitis in cats in which serum fTLI is not increased. In cats, secretin is responsible for stimulation of volume flow and bicarbonate secretion rather than stimulation of enzyme secretion.…”