Modulation of the relationship between amylase and chymotrypsinogen secretion in atropine- and MK329-infused rats

Abstract

We demonstrated previously in ad libitum fed and fasted rats that chymotrypsinogen and amylase secretions were weakly or not at all correlated (1). However, the mechanisms controlling these correlations remain undetermined. We investigated the influences of cholinergic and cholecystokinin-related systems on the relationship between amylase and chymotrypsinogen in rats. Animals provided with pancreatic, biliary, duodenal, and jugular vein cannulas were kept in restraint cages under controlled temperature and humidity, with a regular 12-h light cycle, and divided into five groups. The first group of fed rats was constantly infused with 200 micrograms kg-1 h-1 atropine, the second with 0.5 mg kg-1 h-1 MK329, and the third with both. In the group in which both drugs were simultaneously infused, 500 micrograms kg-1 h-1 atropine was intraperitoneally administered, whereas MK329 was infused by intravenous cannula. Two groups consisted of fasted rats, of which one was also atropinized (100 micrograms kg-1 h-1). Three-day experiments were performed separately with fed rats, and 2-day experiments with fasted rats; atropine and/or MK329 infusion was constant over 48 h, in both fed and fasted rats. Atropine alone did not alter the correlation between enzymes even though the total protein and amylase outputs decreased, whereas the chymotrypsinogen output increased; MK329, slowly but significantly, increased the correlation between enzymes, whereas it decreased the outputs for all secretory parameters. When both antagonists were simultaneously infused in fed rats, correlation coefficients between amylase and chymotrypsinogen rapidly and markedly increased. In fasted rats, atropine infusion induced a tremendous decrease in total protein and amylase mean outputs but a significant increase in chymotrypsinogen output, without any significant change in the correlation between both enzymes. These results indicate that the nonparallel secretion of amylase and chymotrypsinogen is strongly modulated by a cholecystokinin-dependent mechanism and that this modulatory process is potentiated by the parasympathetic system.