Discrepancy between the potency of various trypsin inhibitors to inhibit trypsin activity and the potency to release biologically active cholecystokinin-pancreozymin.

Injection of various trypsin inhibitors into the lumen of the isolated perfused rat duodenum increased the amount of biologically active cholecystokinin-pancreozymin (CCK-BA) in the vascular perfusate. The potency to induce CCK-BA release of the various trypsin inhibitors differed. Injection of ethyl p-(6-guanidinohexanoyloxy) benzoate methanesulfonate (FOY-007; 100 mumol), p-ethoxy-carbamoyl-thio-6-guanidino caproate phosphate (FOY-129; 110 mumol), 4-(4-guanidino-benzoyloxy) phenylacetic acid (FOY-251; 128 mumol), N,N-dimethyl-carbamoylmethyl-4-(4-guanidinobenzoyloxy) phenylacetate methanesulfonate (FOY-305; 80 mumol), and p-aminobenzamidine dihydrochloride (p-ABA, Sigma; 300 mumol) caused release of CCK-BA amounting to 1,042, 247, 252, 682, and 302 pM, respectively. The potency to induce CCK-BA release was not correlated with the potency to inhibit trypsin activity. The present results do not support the hypothesis that a negative feed-back regulation of pancreatic enzyme secretion is exerted by intraluminal trypsin in the rat.