Cholecystokinin is a physiological regulator of gastric acid secretion in man

Abstract

CCK8 is a poor stimulant of gastric acid secretion in vivo, but is equipotent to gastrin-17 (G17) in in vitro systems. To further evaluate the role of cholecystokinin (CCK) in regulating acid output in humans, dose-response curves were constructed to CCK8 or G17 (6.4-800 pmol kg-1 per h) with and without a specific CCK-A receptor antagonist (loxiglumide). During loxiglumide infusion, G17-stimulated acid output was unchanged, whereas CCK8-stimulated secretion increased significantly. Gastric somatostatin-14 release increased fivefold with CCK8 alone, but was blocked with loxiglumide administration. These data suggest that CCK8 directly stimulates acid secretion by binding to a CCK-B/gastrin receptor on parietal cells, but at the same time inhibits acid responses by stimulating gastric somatostatin release to a CCK-A receptor-mediated pathway. To test which action of CCK is relevant under physiological circumstances, the effect of loxiglumide on fasting and post-prandial acidity was measured through continuous pH-metry. After eating, gastrin levels increased fourfold compared to controls with concomitant increases in acid secretion. These results suggest that post cibum, CCK is an inhibitor of acid secretion by regulating gastrin through local somatostatin; they support the hypothesis that CCK acts as an enterogastrone.

The G Cell

“…It also provides the mechanism for many of the indirect effects of other hormones on gastrin release. For example, CCK released from the small bowel during the intestinal phase of digestion does not have a direct effect on the G cell but rather enhances somatostatin secretion via CCK A receptors on D cells (9,18,104), which inhibits gastrin release. In a similar fashion, secretin, gastric inhibitory polypeptide, prostaglandin E2, and glucagon also stimulate the release of somatostatin and inhibit gastrin secretion (14,54,100).…”

The effects of vapreotide, a somatostatin analogue, on gastric acidity, gallbladder emptying and hormone release after 1 week of continuous subcutaneous infusion in normal subjects

“…Intragastric pH measurements were recorded every 6 s over 24 h. Median pH value was calculated for each subject as previously described [ 13]. Distribution of these values was characterised for each treatment group by median pH as well as 5th, 25th, 75th and 95th percentiles and the data are presented as box Whisker plots.…”

Cholecystokinin as a physiological regulator of gastric acid secretion in man

“…Since then the genes encoding human CCK, and the human CCK-A and CCK-B receptors have been cloned [4], greatly advancing understanding of how CCK acts, and where. Specific CCK-receptor antagonists have been the other vital tool [5,6].…”

“…We recently used this method to show diminished somatostatin expression in patients with achlorhydria [I 13, supporting the idea that luminal acid inhibits gastric function by stimulating D-cells. Another approach is to use agonists and antagonists of the receptors present on D-cells, as in the study by Burckhardt et al [6]. One recent study used gastrin, CCK and a CCK-A receptor antagonist to study canine fundic D-cells in primary culture.…”