Comparative effects of CCK-8 on feeding, sham feeding, and exocrine pancreatic secretion in rats

Cholecystokinin (CCK) is thought to be a hormonal regulator of exocrine pancreatic secretion and is postulated to be a satiety hormone. We compared the dose-response effects of CCK octapeptide (CCK-8) on feeding, sham feeding, and pancreatic secretion to gauge whether the feeding effect might be physiological. Pancreatic responses to intravenous CCK-8 (40, 200, 1,000, or 4,000 pmol . kg-1 . h-1) in fasted unanesthetized rats were compared with effects of CCK-8 (0, 200, 1,000, or 4,000 pmol . kg-1 . h-1) on ingestion of liquid diet in fasted rats with gastric cannulas either closed (normal feeding) or open (sham feeding). Maximal pancreatic amylase output occurred at 200 pmol . kg-1 . h-1 of CCK-8; output declined at higher doses. Food intake was significantly inhibited only at 1,000 and 4,000 pmol . kg-1 . h-1 of CCK-8; the effect was similar when gastric cannulas were closed and open. These results, together with available data on the low postprandial levels of plasma CCK, suggest that circulating levels of CCK normally present after food intake are not sufficient to produce satiety. Furthermore, suppression of feeding by CCK does not appear to be mediated solely by a mechanism that senses gastric distension, because CCK-8 had similar effects in the presence and absence of gastric distension. Whether CCK interacts with other neural or humoral factors to produce satiety by a hormonal mechanism remains to be determined.