Regulation of enterokinase synthesis in animal and human small intestine by luminal signals: its implication in upper gastrointestinal surgery.

Enterokinase is an enzyme produced by the mucosa of the small intestine. Its sole function is to activate trypsinogen to trypsin. In animals and man the duodenum and proximal jejunum have high levels of activity whereas the remaining small bowel has minimal levels. A reproducible assay was developed for measuring mucosal enterokinase activity applicable to operative and endoscopic biopsies. Anaesthetic and operative techniques were developed for small intestinal resections in guinea-pigs to ensure their long term survival. Transposition of high-enterokinase-secreting segments of guinea-pig small intestine to low-enterokinase regions and vice versa showed no alteration of enterokinase activity in the transposed segments. Similarly, resection of the enterokinase region in five proximal pancreaticoduodenectomy operations in man revealed no induction of enterokinase in the remaining jejunum at endoscopy 6 months later. Isolation of high-enterokinase-secreting segments of small bowel from their luminal continuity by fashioning of Thiry--Vella fistulas led to a decay of enterokinase activity to minimal levels within 12--16 h. Perfusion of these fistulas with trypsin and sodium, or chymotrypsin and sodium, prevented this decay. If the enterokinase was allowed to decay over 24 h its activity could be restored to 80 per cent of its normal level by perfusion for 24 h with trypsin and sodium. Trypsin and sodium acti in combination on an enterocyte membrane receptor to stimulate enterokinase synthesis.