EVIDENCE FOR INDIRECT DIETARY-REGULATION OF CHOLECYSTOKININ RELEASE IN RATS

Food ingestion stimulates cholecystokinin (CCK) release from the proxi mal intestine, but the mechanisms involved are not well understood. To investigate this effect in vivo in intact rats, plasma CCK was measur ed after orogastric feeding of proteins, protein hydrolysates, amino a cids, glucose, and starch. Intact proteins were the only nutrients to stimulate CCK release. The possibility of direct interaction between d ifferent dietary constituents and intestinal CCK-secreting endocrine c ells was then examined using a perifusion system containing isolated m ucosal cells from the rat duodenojejunum. The functional validity of t his system was established by demonstrating that monitor peptide and b ombesin both stimulated CCK release in a dose-dependent manner. The st imulatory effect of bombesin required extracellular calcium and was no t inhibited by addition of tetrodotoxin. Perifusion of proteins, prote in digests, and carbohydrates did not stimulate CCK release. These res ults indicate that proteins stimulate CCK release postprandially via a n indirect mechanism, most likely related to inhibition of intralumina l trypsin. Perifusion of dispersed mucosal cells constitutes a reprodu cible model to investigate hormonal and peptidergic regulation of CCK release in vitro.