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Proteinase Inhibitors Induce Selective Stimulation of Human Trypsin and Chymotrypsin Secretion^1,2,

Janne E. Reseland, Halvor Holm^*,3, Morten B. Jacobsen, Trond G. Jenssen^** and Lars E. Hanssen

MATFORSK, Norwegian Food Research Institute, N-1430 Ås, and Biotechnology Centre of Oslo, University of Oslo, Norway ^* Institute for Nutrition Research, University of Oslo, N-0316 Oslo, Norway Medical Department A, Rikshospitalet, N-0027 Oslo, Norway Medical Department, University Hospital of Tromsø, N-9012 Tromsø, Norway

Among the variety of signals stimulating pancreatic secretion, cholecystokinin (CCK) and related hormones are assumed to be responsible for modulating proteinase output. In some species, intraduodenal tryptic activity has to be abolished to demonstrate feedback-induced CCK release. The aim of this study was to investigate in vivo effects of modest inhibition of intraduodenal proteolytic enzymes on the secretion patterns of pancreatic enzymes and plasma CCK concentrations. Two inhibitors (Kunitz trypsin inhibitor and Bowman-Birk inhibitor) were applied. Intermittent sampling of plasma and duodenal juice was performed during intraduodenal saline and inhibitor instillations in six healthy volunteers. Enzyme activities and concentrations were determined in the duodenal samples and expressed as percentages of basal values. Instillation of Kunitz trypsin inhibitor caused an increase in trypsin and the pancreatic secretory trypsin inhibitor (PSTI), without changes in plasma CCK. This result demonstrates, for the first time, that pancreatic exocrine secretion of trypsin and chymotrypsin is regulated by different mechanisms. Bowman-Birk inhibitor additionally stimulated the secretion of chymotrypsin and carboxypeptidase A and B and increased plasma CCK. Elastase 1 and amylase secretions were not increased by either instillations. Although the inhibitors have similar in vitro inhibition patterns, their in vivo effects are different. The nonparallel secretion of proteinases (trypsin, chymotrypsin and elastase 1) supports the view of a complex system involved in feedback regulation of human pancreatic exocrine secretion, including signals other than CCK.

KEY WORDS: • cholecystokinin release • feed-back regulation • pancreatic secretion • proteinases • soybean inhibitors • humans

¹ The present study received financial support from The Research Council of Norway, Norwegian Dairies (J. E. Reseland), FREIA Chocolate Factory Medical Foundation (H. Holm) and The Norwegian Cancer Society (L. E. Hanssen).

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ To whom correspondence should be addressed.

Manuscript received 15 June 1994. Revision accepted 6 November 1995.