Cholecystokinin is a negative regulator of gastric acid secretion and postprandial release of gastrin in humans.
OBJECTIVE
The role of cholecystokinin (CCK) in the regulation of gastric acid secretion is still controversial. This study examined the effect of the CCK-A receptor antagonist loxiglumide (lox) on gastrin- or CCK-induced gastric acid secretion and meal-stimulated plasma gastrin levels in a placebo-controlled study.


METHODS
Acid output was studied in eight subjects who received intravenously gastrin-17 (15, 30, and 60 pmol.kg-1.h-1); gastrin-17 plus lox; cholecystokinin octapeptide (CCK-8) (15, 30, and 60 pmol.kg-1.h-1); CCK-8 plus lox; or gastrin plus CCK-8. Sham feeding-induced acid output and meal-stimulated gastrin secretion were studied during lox infusion.


RESULTS
Gastrin-17 dose-dependently stimulated acid output to near-maximal levels. CCK-8 (15 pmol.kg-1.h-1) increased acid secretion 2.5-fold over basal; higher infusion rates had less or no effect. When combined with lox, CCK-8 produced a near-maximal acid response (6-fold over basal). CCK-8 together with gastrin-17 inhibited gastrin-induced acid output by 67%. Meal-stimulated plasma gastrin concentrations were elevated 3.2-fold, whereas sham feeding-induced acid secretion was not modified by lox.


CONCLUSIONS
Blockade of CCK-A receptors converts CCK-8 into a potent acid secretagogue and augments postprandial gastrin secretion. A CCK-mediated stimulation of paracrine somatostatin secretion from antral and fundic D cells represents a candidate mechanism for the inhibition of the parietal and gastrin cell in humans.
First Department of Medicine, Christian-Albrechts-University, Kiel, Germany.
W E
WE
Schmidt
S
S
Schenk
R
R
Nustede
J J
JJ
Holst
U R
UR
Fölsch
W
W
Creutzfeldt
D000328:Adult; D002766:Cholecystokinin / Q000494:pharmacology / Q000502:physiology*; D004435:Eating; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008297:Male; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology; D011863:Radioimmunoassay; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D013004:Somatostatin / Q000097:blood; D013270:Stomach / Q000187:drug effects
D005755:Gastrins; D011949:Receptors, Cholecystokinin; D013004:Somatostatin; C053737:loxiglumide; D002766:Cholecystokinin; D011377:Proglumide