INTERACTIONS OF PANCREATIC SECRETORY TRYPSIN-INHIBITOR IN SMALL INTESTINAL JUICE - ITS HYDROLYSIS AND PROTECTION BY INTRALUMINAL FACTORS

It has been proposed that modulation of cholecystokinin (CCK) release by proteinases, proteinase inhibitors and protein is mediated by a pancreatic secretory trypsin inhibitor (PSTI), also called monitor peptide, in the rat. When human [I-125]-PSTI was incubated with fasting small bowel juice or activated pancreatic juice > 88% of tracer eluted from gel chromatography in the characteristic position of hydrolysed PSTI. However, when the small bowel juice had been preincubated with soybean trypsin inhibitor 3 g/l, casein 5 g/l or lactalbumin 30 g/l, the hydrolysis of PSTI diminished so that 95%, 32%, and 33% respectively, now eluted in the characteristic position of free (i.e. intact and not bound to an enzyme) PSTI. When [I-25]-PSTI was incubated with pure trypsin, chymostrypsin, elastase or enterokinase > 95% of tracer eluted in the position of PSTI-enzyme complex. Incubation of PSTI with trypsin plus one other enzyme was required to produce hydrolysis. The degree of protection of PSTI from hydrolysis in duodenal juice produced by the substances correlates with their effects on CCK release. Our findings support the hypothesis that PSTIs mediate the modulation of CCK release by intraluminal proteinases, proteinase inhibitors and proteins.