STABILITY OF CIRCADIAN AND MINOR CYCLES OF EXOCRINE PANCREATIC-SECRETION IN ATROPINE-INFUSED AND MK-329-INFUSED RATS

We previously demonstrated the existence of a circadian rhythm of panc reatic secretion of fluid and digestive enzymes, which was superimpose d on by a regular 1.84-h minor cycle of exocrine pancreatic secretion of fluid and total protein, amylase, and chymotrypsinogen (25). Direct control of these daily and hourly rhythms of pancreatic secretory fun ction has not been addressed. Cholinergic and cholecystokinin (CCK)-as sociated influences on these two rhythms of exocrine pancreatic secret ion were investigated in rats provided with pancreatic, biliary, duode nal, and jugular vein cannulas, allowing separate drainage of bile and pure pancreatic juice, as well as intravenous infusions of atropine s ulfate and/or MK-329. Rats were kept in restraint cages under controll ed temperature and humidity, with a regular 12-h light cycle, and divi ded into five groups. The first group of fed rats was constantly infus ed with 200 mu g.kg(-1).h(-1) atropine, the second with 0.5 mg.kg(-1). h(-1) MK-329, and the third with both. In the group where both drugs w ere simultaneously infused, 500 mu g.kg(-1).h(-1) atropine was intrape ritoneally administered, whereas MK-329 was infused by intravenous can nula. Two groups consisted of fasted rats, of which one was also given atropine (100 mu g.kg(-1).h(-1)). Three-day experiments were performe d separately with fed rats, and 2-day experiments were performed with fasted rats; atropine and/or MK-329 infusion, starting on day 2, was c onstant over 48 h in both fed and fasted rats. Atropine decreased flui d, total protein, and amylase outputs, whereas chymotrypsinogen output increased; in MK-329-infused rats, significant decreases were observe d for all secretory parameters. When both antagonists were simultaneou sly infused in fed rats, total mean outputs for all secretory paramete rs decreased after the MK-329-induced tendency. In fasted rats, atropi ne infusion decreased fluid, total protein, and amylase mean outputs, but chymotrypsinogen output significantly increased. Even though total mean outputs significantly changed under drug infusion, pancreatic se cretion rose in the dark period and fell in the light period in fasted as well as in ad libitum-fed rats. Atropine and MK-329 did not signif icantly alter the overall pattern of minor cycles of pancreatic secret ion even though total mean outputs markedly changed. The stability of the rhythm of minor-cycle peak intervals in antagonist-infused rats su ggests that the 1.8-h cycle of pancreatic secretion is independent of both cholinergic and CCK-related mechanisms, even though these antagon ists have clear effects on overall secretory outputs.