Isolation and Bioactivity of Putative Cholecystokinin-Releasing Reptide From rat Small Intenstinal Mucosa

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Paiicreatic exocrine secretion in the conscious rat is regulated by proteases in the intestine secreted by the pancreas, and cholecystokinin (CCK) is known to be involved in the mechanism. We proposed that the release of CCK was regulated by a CCK-releasing factor secreted into the ifitestinal lumen from the proximal intestine. We isolated and partially purified a CCK-releasing factor from rat small intestine by gel filtration and high performance liquid chromatography. The partially purified CCK-releasing factor increased pancreatic exocrine secretions and plasma CCK concentrations in conscious rats and this activity was abolished after the incubation with trypsin. The bioactivity of the partially purified CCK-releasing factor was confirmed. The role of luminal bile salt (taurocholate) in regulation of rat pancreatic secretion was examined by studies on the effects of luminal stimulants on pancreas during infusion of various concentrations of taurocholate into the duodenum of conscious rats. Rats with external bile and pancreatic fistulac were used. 8-200 mM of taurocholate was infused at a rate of 1 ml/h instead of returning the bile. Pancreatic juice was collected for a 2-hour period and then 2 mug of pancreatic secretory trypsin inhibitor-61 (PSTI-61) (= monitor peptide) or partially purified putative CCK releasing peptide from rat intestine (intestinal CCK-RP) was injected into the duodenum (1 ml/min). Continuous infusion of taurocholate maintained a constant rate of pancreatic secretion, except at a concentration of 8 mM, which resulted in slight increase in pancreatic secretion. Both PSTI-61 and intestinal CCK-RP significantly increased pancreatic secretions during infusion of 20 or 40 mM taurocholate, but had no significant effect during, infusion of 80 or 200 mM taurocholate. Therefore, higher concentrations of taurocliolate in the intestine prevented the stimulatory effects of luminal stimulants, probably by preventing the latter from reaching CCK cells.