Loxiglumide inhibits cholecystokinin stimulated somatostatin secretion and simultaneously enhances gastric acid secretion in humans.
In vitro studies have demonstrated that cholecystokinin releases somatostatin from the gastric mucosa. To date, there is no information about the in vivo significance of this finding in man. Therefore, we have studied the effect of infusion of cholecystokinin resulting in plasma concentrations within the range found after meal-stimulation, on somatostatin release and on gastric acid secretion. In addition we have studied these functions during infusion of the type A cholecystokinin receptor antagonist loxiglumide. In eight healthy subjects, basal gastric acid secretion was distinctly stimulated by cholecystokinin. The effect of cholecystokinin on gastric acid secretion was markedly enhanced by loxiglumide. Cholecystokinin also significantly stimulated somatostatin output into the gastric lumen, but not into the systemic circulation. Somatostatin output into the gastric lumen during infusion of cholecystokinin was abolished by loxiglumide. The data indicate that on the one hand circulating cholecystokinin, like gastrin, stimulates gastric acid secretion probably by binding to less specific type B receptors on parietal cells that are not blocked by loxiglumide, but on the other hand that cholecystokinin, in contrast to gastrin, also inhibits gastric acid secretion probably by binding to specific type A receptors present on somatostatin producing D-cells in the gastric mucosa, that are blocked by loxiglumide.
Department of Gastroenterology and Hepatology, University Hospital St. Radboud, Nijmegen, The Netherlands.
M L
ML
Verhulst
H A
HA
Gielkens
W P
WP
Hopman
A
A
van Schaik
A
A
Tangerman
L C
LC
Rovati
J B
JB
Jansen
D000328:Adult; D002766:Cholecystokinin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D011377:Proglumide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D013004:Somatostatin / Q000378:metabolism*; D013997:Time Factors
D011949:Receptors, Cholecystokinin; D013004:Somatostatin; C053737:loxiglumide; D002766:Cholecystokinin; D011377:Proglumide