ELEVATION OF CIRCULATING MONITOR PEPTIDE PANCREATIC SECRETORY TRYPSININHIBITOR-I (PSTI-61) AFTER TURPENTINE-INDUCED INFLAMMATION IN RATS -HEPATOCYTES PRODUCE IT AS AN ACUTE-PHASE REACTANT/

Monitor peptide (RIP) is a trypsin-sensitive cholecystokinin (CCK)-rel easing peptide purified from rat pancreatic juice on the basis of its stimulatory activity toward pancreatic enzyme secretion and has been r eported to exhibit cell growth-stimulating activity. Pancreatic secret ory trypsin inhibitor (PSTI) prevents premature activation of trypsino gen in the pancreatic duct. There are two PSTIs (PSTI-61 and -56) puri fied from rat pancreatic juice on the basis of trypsin inhibitory acti vity as reported previously. Fushiki ct al. (1989, FASEB J. 3, 121) sh owed that MP is structually the same peptide as PSTI-61. We measured t he serial changes of circulating MP/PSTI-61 in rat and those in the le vel of PSTI-61 mRNA in the rat liver to investigate another novel role of this peptide in the turpentine-induced acute inflammation model. T he elevation of serum MP/PSTI-61 as well as the alpha(2)-globulin frac tion, which is known to include several acute phase reactants such as alpha(2)-macroglobulin and haptoglobin, was observed after induction o f the turpentine inflammation. The serum alpha(2)-globulin fraction ha d increased approximately 3-fold over the initial level at 48 hr after the injection. In contrast, serum MP/PSTI-61 had increased approximat ely 17-fold over the initial level at 48 hr after the injection. The e levation of circulating MP/PSTI-61 was significantly related with that of the alpha(2)-globulin fraction (r = 0.91, P < 0.01). Immunoreactiv e MP/PSTI-61 was detected in the liver after induction of the inflamma tion (152.5 +/- 16.5 ng/g wet weight), but in the normal rat liver the re was no immunoreactive MP/PSTI-61. Furthermore, the elevated express ion of PSTI-61 mRNA was only detected in the liver, using a synthetic oligonucleotide probe specific for PSTI-61. These results demonstrate that rat MP/PSTI-61 is produced as an acute phase reactant in the live r in response to inflammatory stimuli, as well as other known acute ph ase reactants such as alpha(2)-macroglobulin and haptoglobin, (C) 1994 Academic Press, Inc.