INHIBITOR-STIMULATED NONPARALLEL PANCREATIC-SECRETION IN MAN - HORMONAL AND NEURAL REGULATION

Background: We wanted to study whether a total inhibition of tryptic a ctivity in the duodenum would induce a cholecystokinin (CCK)-dependent increase in pancreatic exocrine proteinase secretion. Methods: Concen trations of CCK and activities and concentrations of pancreatic enzyme s were measured in human plasma and duodenal juices, respectively, col lected during continuous intraduodenal instillations of proteinase inh ibitors, with and without intravenous atropine administration. Results : Inhibitor instillation totally abolished tryptic activity and reduce d the chymotryptic and elastase (1 and 2) activities by 95-100%. The i nhibitors caused a rapid increase in the concentrations of trypsin, ch ymotrypsin, and pancreatic secretory trypsin inhibitor (PSTI) but had only a slight or no effect on amylase and elastase 1 secretion. An enh anced secretion of PSTI lends support to a possible connection between PSTI (resembling the monitor peptide causing CCK release in rats) and the enzyme secretion in man. CCK increased from 7 to 12-13 pmol/l. In travenous atropine almost completely blocked the inhibitor-stimulated enzyme and PSTI secretion and reduced amylase activity by 50%. A furth er significant (P = 0.002) increase in the inhibitor-induced CCK outpu t was found during atropine administration, as compared with the test situation without atropine. Conclusion: The inhibitor-induced pancreat ic secretion during total inhibition of tryptic activity shows a non-p arallel secretion requiring different signals for different enzymes. T he increase in plasma CCK levels indicates that CCK is feedback-regula ted by both an inhibitor-mediated decrease in duodenal enzyme activity and a further decrease in pancreatic enzyme secretion by atropine.