PROTEINASE-INHIBITORS INDUCE SELECTIVE STIMULATION OF HUMAN TRYPSIN AND CHYMOTRYPSIN SECRETION

Among the variety of signals stimulating pancreatic secretion, cholecy stokinin (CCK) and related hormones are assumed to be responsible for modulating proteinase output. In some species, intraduodenal tryptic a ctivity has to be abolished to demonstrate feedback-induced CCK releas e. The aim of this study was to investigate in vivo effects of modest inhibition of intraduodenal proteolytic enzymes on the secretion patte rns of pancreatic enzymes and plasma CCK concentrations. Two inhibitor s (Kunitz trypsin inhibitor and Bowman-Birk inhibitor) were applied. I ntermittent sampling of plasma and duodenal juice was performed during intraduodenal saline and inhibitor instillations in six healthy volun teers. Enzyme activities and concentrations were determined in the duo denal samples and expressed as percentages of basal values. Instillati on of Kunitz trypsin inhibitor caused an increase in trypsin and the p ancreatic secretory trypsin inhibitor (PSTI), without changes in plasm a CCK. This result demonstrates, for the first time, that pancreatic e xocrine secretion of trypsin and chymotrypsin is regulated by differen t mechanisms. Bowman-Birk inhibitor additionally stimulated the secret ion of chymotrypsin and carboxypeptidase A and B and increased plasma CCK. Elastase 1 and amylase secretions were not increased by either in stillations. Although the inhibitors have similar in vitro inhibition patterns, their in vivo effects are different. The nonparallel secreti on of proteinases (trypsin, chymotrypsin and elastase 1) supports the view of a complex system involved in feedback regulation of human panc reatic exocrine secretion, including signals other than CCK.