Cholecystokinin is a physiological regulator of gastric acid secretion in man.
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.
Burckhardt
B
B
Division of Gastroenterology, University Hospital, Basel, Switzerland.
Delco
F
F
Ensinck
J W
JW
Meier
R
R
Bauerfeind
P
P
Aufderhaar
U
U
Ketterer
S
S
Gyr
K
K
Beglinger
C
C
D000328:Adult; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004435:Eating; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects*; D005755:Gastrins / Q000097:blood / Q000494:pharmacology*; D006706:Homeostasis; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D012844:Sincalide / Q000494:pharmacology*; D013004:Somatostatin / Q000378:metabolism
D005755:Gastrins; D006728:Hormones; D013004:Somatostatin; C013550:gastrin 17; C053737:loxiglumide; D002766:Cholecystokinin; D011377:Proglumide; D012844:Sincalide